Search Results

Overview

Uniprot IDQ04828
Protein NameAldo-keto reductase family 1 member C1
Gene NameAKR1C1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
123 IHFPVSVKPGEEVIP
155 WEAVEKCKDAGLAKS
161 CKDAGLAKSIGVSNF
179 QLEMILNKPGLKYKP
183 ILNKPGLKYKPVCNQ
185 NKPGLKYKPVCNQVE
201 HPYFNQRKLLDFCKS
207 RKLLDFCKSKDIVLV
209 LLDFCKSKDIVLVAY
246 PVLCALAKKHKRTPA
270 RGVVVLAKSYNEQRI
31 YAPAEVPKSKALEAT
33 PAEVPKSKALEATKL
39 SKALEATKLAIEAGF
4 ****MDSKYQCVKLN
68 VGLAIRSKIADGSVK
75 KIADGSVKREDIFYT
84 EDIFYTSKLWCNSHR
9 DSKYQCVKLNDGHFM

Function

Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids. Displays broad substrate specificity with distinct positional and stereochemistry, primarily generating 20alpha-hydroxysteroids, but also 3alpha/beta- and 17beta-hydroxysteroids (PubMed:10998348, PubMed:11013348, PubMed:14672942, PubMed:19218247, PubMed:11995921, PubMed:12604236). Involved in neurosteroid metabolism. Reduces 5alpha-dihydrodeoxycorticosterone (5-alpha-DHDOC) to neuroactive steroid 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) known to alter neural excitability via allosteric activation of gamma-aminobutyric acid type A (GABAAR) receptors. Inactivates 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) into less potent neurosteroid 3alpha,20alpha-dihydroxy-5alpha-pregnane (PubMed:11995921, PubMed:12604236). Catalyzes the reduction of progesterone to less potent progestogen (20S)-hydroxypregn-4-en-3-one likely regulating ligand availability for progesterone receptors (PubMed:10998348, PubMed:11013348, PubMed:12604236). In androgen catabolism, may predominantly act as a phase I enzyme by introducing a hydroxyl group prior to conjugation. It can nevertheless participate in the alternative phase II pathway by directly reducing sulfate- or glucuronide-conjugated androgens (PubMed:19218247). In vitro can efficiently catalyze bidirectional conversion between ketosteroids and hydroxysteroids using NADPH/NADP(+) or NADH/NAD(+) as cofactors. In vivo however, the reductase activity prevails since the major reducing cofactor NADPH inhibits NAD(+)-dependent oxidase activity (PubMed:14672942)

Protein Sequence

10 MDSKYQCVKL 20 NDGHFMPVLG 30 FGTYAPAEVP 40 KSKALEATKL 50 AIEAGFRHID 60 SAHLYNNEEQ 70 VGLAIRSKIA 80 DGSVKREDIF 90 YTSKLWCNSH 100 RPELVRPALE 110 RSLKNLQLDY 120 VDLYLIHFPV 130 SVKPGEEVIP 140 KDENGKILFD 150 TVDLCATWEA 160 VEKCKDAGLA 170 KSIGVSNFNR 180 RQLEMILNKP 190 GLKYKPVCNQ 200 VECHPYFNQR 210 KLLDFCKSKD 220 IVLVAYSALG 230 SHREEPWVDP 240 NSPVLLEDPV 250 LCALAKKHKR 260 TPALIALRYQ 270 LQRGVVVLAK 280 SYNEQRIRQN 290 VQVFEFQLTS 300 EEMKAIDGLN 310 RNVRYLTLDI 320 FAGPPNYPFS DEY

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0070062 extracellular exosome
Molecular Function GO:0047006 17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase [NAD(P)+] activity
Molecular Function GO:0140169 3-alpha-hydroxysteroid 3-dehydrogenase [NAD(P)+] activity
Molecular Function GO:0033703 3-beta-hydroxy-5-beta-steroid dehydrogenase (NADP+) activity
Molecular Function GO:0000253 3-beta-hydroxysteroid 3-dehydrogenase (NADP+) activity
Molecular Function GO:0047024 5-alpha-androstane-3-beta,17-beta-diol dehydrogenase (NADP+) activity
Molecular Function GO:0008106 alcohol dehydrogenase (NADP+) activity
Molecular Function GO:0004032 aldose reductase (NADPH) activity
Molecular Function GO:0047044 androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity
Molecular Function GO:0047023 androsterone dehydrogenase [NAD(P)+] activity
Molecular Function GO:0032052 bile acid binding
Molecular Function GO:0031406 carboxylic acid binding
Molecular Function GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity
Molecular Function GO:0047718 indanol dehydrogenase activity
Molecular Function GO:0047086 ketosteroid monooxygenase activity
Molecular Function GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
Molecular Function GO:0033764 steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Molecular Function GO:0047045 testosterone dehydrogenase (NADP+) activity
Molecular Function GO:0047115 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Biological Process GO:0015721 bile acid and bile salt transport
Biological Process GO:0008206 bile acid metabolic process
Biological Process GO:0071395 cellular response to jasmonic acid stimulus
Biological Process GO:0042632 cholesterol homeostasis
Biological Process GO:0044597 daunorubicin metabolic process
Biological Process GO:0007586 digestion
Biological Process GO:0044598 doxorubicin metabolic process
Biological Process GO:0030855 epithelial cell differentiation
Biological Process GO:0030299 intestinal cholesterol absorption
Biological Process GO:2000379 positive regulation of reactive oxygen species metabolic process
Biological Process GO:0042448 progesterone metabolic process
Biological Process GO:0006693 prostaglandin metabolic process
Biological Process GO:0042574 retinal metabolic process
Biological Process GO:0001523 retinoid metabolic process
Biological Process GO:0006805 xenobiotic metabolic process

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.