Akr1c21 aldo-keto reductase family 1, member C21 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Akr1c21provided by MGI
Official Full Name: aldo-keto reductase family 1, member C21provided by MGI
Primary source: MGI:MGI:1924587
See related: Ensembl:ENSMUSG00000021207 AllianceGenome:MGI:1924587
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: 9430025F20Rik
Summary: Enables NADP binding activity; lithocholic acid binding activity; and steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Involved in steroid metabolic process. Predicted to be located in cytoplasm and nucleus. Predicted to be active in cytosol. Human ortholog(s) of this gene implicated in 46,XY sex reversal 8; B-lymphoblastic leukemia/lymphoma; T-cell acute lymphoblastic leukemia; and leukemia. Orthologous to several human genes including AKR1C1 (aldo-keto reductase family 1 member C1); AKR1C2 (aldo-keto reductase family 1 member C2); and AKR1C3 (aldo-keto reductase family 1 member C3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Restricted expression toward kidney adult (RPKM 66.8) See more
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Genomic context

Location:: 13 A1; 13 2.56 cM

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	13	NC_000079.7 (4624074..4636542)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	13	NC_000079.6 (4574075..4586543)

Chromosome 13 - NC_000079.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

mutation resulted in a change in the conformation of the flexible loop B, including the V-shaped groove, which is a unique feature of the active-site architecture of wild-type AKR1C21 and is formed by the side chains of Tyr224 and Trp227.
Title: Studies on a Tyr residue critical for the binding of coenzyme and substrate in mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21): structure of the Y224D mutant enzyme.
Gly225 & Gly226 help determine the substrate stereospecificity. The G225P/G226P mutation reduced the affinity for both 3alpha- & 17alpha-hydroxysteroid substrates by up to 160-fold, indicating that these residues are critical for substrate binding.
Title: Structure of the G225P/G226P mutant of mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) ternary complex: implications for the binding of inhibitor and substrate.
X-ray diffraction analysis of mouse 3(17)alpha-hydroxysteroid dehydrogenase
Title: Crystallization and preliminary X-ray diffraction analysis of mouse 3(17)alpha-hydroxysteroid dehydrogenase.
crystal structure of the m17alpha-HSD enzyme in its apo-form (1.9 A resolution) as well as those of two different forms of this enzyme in binary complex with NADP(H) (2.9 A and 1.35 A resolution)(
Title: Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase (apoenzyme and enzyme-NADP(H) binary complex): identification of molecular determinants responsible for the unique 17alpha-reductive activity of this enzyme.
study reports a ternary complex crystal structure (m17alpha-HSD:NADP(+):epi-T) determined at 1.85 A resolution reveals a unique steroid-binding mode for an AKR enzyme
Title: Mouse 17alpha-hydroxysteroid dehydrogenase (AKR1C21) binds steroids differently from other aldo-keto reductases: identification and characterization of amino acid residues critical for substrate binding.

Submit: New GeneRIF Correction

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (1)

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables 17-beta-hydroxysteroid dehydrogenase (NADP+) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables 17-beta-ketosteroid reductase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables 5alpha-androstane-3beta,17beta-diol dehydrogenase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables NADP+ binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables NADPH binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables aldo-keto reductase (NADPH) activity	ISA Inferred from Sequence Alignment more info	PubMed
enables aldose reductase (NADPH) activity	IBA Inferred from Biological aspect of Ancestor more info
enables aldose reductase (NADPH) activity	ISO Inferred from Sequence Orthology more info
enables androsterone dehydrogenase (B-specific) activity	ISO Inferred from Sequence Orthology more info
enables androsterone dehydrogenase activity	IDA Inferred from Direct Assay more info	PubMed
enables androsterone dehydrogenase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables androsterone dehydrogenase activity	ISO Inferred from Sequence Orthology more info
enables bile acid binding	ISO Inferred from Sequence Orthology more info
enables carboxylic acid binding	ISO Inferred from Sequence Orthology more info
enables chlordecone reductase activity	ISO Inferred from Sequence Orthology more info
enables ketosteroid monooxygenase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ketosteroid monooxygenase activity	ISO Inferred from Sequence Orthology more info
enables lithocholic acid binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	ISO Inferred from Sequence Orthology more info
enables phenanthrene 9,10-monooxygenase activity	ISO Inferred from Sequence Orthology more info
enables retinal dehydrogenase activity	ISO Inferred from Sequence Orthology more info
enables steroid binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables steroid dehydrogenase activity	IBA Inferred from Biological aspect of Ancestor more info
enables steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IDA Inferred from Direct Assay more info	PubMed
enables steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IMP Inferred from Mutant Phenotype more info	PubMed
enables trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in cellular response to jasmonic acid stimulus	ISO Inferred from Sequence Orthology more info
involved_in daunorubicin metabolic process	ISO Inferred from Sequence Orthology more info
involved_in doxorubicin metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lipid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within steroid biosynthetic process	ISA Inferred from Sequence Alignment more info	PubMed
involved_in steroid metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in steroid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: aldo-keto reductase family 1 member C21

Names: 17-alpha-HSD; 17-alpha-hydroxysteroid dehydrogenase; 3(17)alpha-hydroxysteroid dehydrogenase; 3(or 17)-alpha-hydroxysteroid dehydrogenase; 3-alpha-hydroxysteroid dehydrogenase; DD1; DD3; dihydrodiol dehydrogenase type 1; dihydrodiol dehydrogenase type 3

NP_084177.2

EC 1.1.1.209

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.