LOCUS       NM_001818               1192 bp    mRNA    linear   PRI 21-SEP-2024
DEFINITION  Homo sapiens aldo-keto reductase family 1 member C4 (AKR1C4), mRNA.
ACCESSION   NM_001818
VERSION     NM_001818.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1192)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   2  (bases 1 to 1192)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Paulo,J.A., Cannon,J.R., Ting,L.,
            Baltier,K., Colby,G., Gebreab,F., Gygi,M.P., Parzen,H., Szpyt,J.,
            Tam,S., Zarraga,G., Pontano-Vaites,L., Swarup,S., White,A.E.,
            Schweppe,D.K., Rad,R., Erickson,B.K., Obar,R.A., Guruharsha,K.G.,
            Li,K., Artavanis-Tsakonas,S., Gygi,S.P. and Harper,J.W.
  TITLE     Architecture of the human interactome defines protein communities
            and disease networks
  JOURNAL   Nature 545 (7655), 505-509 (2017)
   PUBMED   28514442
REFERENCE   3  (bases 1 to 1192)
  AUTHORS   Shiiba,M., Yamagami,H., Yamamoto,A., Minakawa,Y., Okamoto,A.,
            Kasamatsu,A., Sakamoto,Y., Uzawa,K., Takiguchi,Y. and Tanzawa,H.
  TITLE     Mefenamic acid enhances anticancer drug sensitivity via inhibition
            of aldo-keto reductase 1C enzyme activity
  JOURNAL   Oncol Rep 37 (4), 2025-2032 (2017)
   PUBMED   28259989
  REMARK    GeneRIF: the present study suggests that AKR1C1, AKR1C2, AKR1C3,
            and AKR1C4 are closely associated with drug resistance to both CDDP
            and 5FU, and that mefenamic acid, an inhibitor of AKR1C, restores
            sensitivity through inhibition of drug-resistance in human cancer
            cells.
REFERENCE   4  (bases 1 to 1192)
  AUTHORS   Shin,S.Y., Fauman,E.B., Petersen,A.K., Krumsiek,J., Santos,R.,
            Huang,J., Arnold,M., Erte,I., Forgetta,V., Yang,T.P., Walter,K.,
            Menni,C., Chen,L., Vasquez,L., Valdes,A.M., Hyde,C.L., Wang,V.,
            Ziemek,D., Roberts,P., Xi,L., Grundberg,E., Waldenberger,M.,
            Richards,J.B., Mohney,R.P., Milburn,M.V., John,S.L., Trimmer,J.,
            Theis,F.J., Overington,J.P., Suhre,K., Brosnan,M.J., Gieger,C.,
            Kastenmuller,G., Spector,T.D. and Soranzo,N.
  CONSRTM   Multiple Tissue Human Expression Resource (MuTHER) Consortium
  TITLE     An atlas of genetic influences on human blood metabolites
  JOURNAL   Nat Genet 46 (6), 543-550 (2014)
   PUBMED   24816252
REFERENCE   5  (bases 1 to 1192)
  AUTHORS   Rizner,T.L. and Penning,T.M.
  TITLE     Role of aldo-keto reductase family 1 (AKR1) enzymes in human
            steroid metabolism
  JOURNAL   Steroids 79, 49-63 (2014)
   PUBMED   24189185
  REMARK    GeneRIF: Studies indicate that mutations in aldo-keto reductase
            family 1 (AKR1) enzymes AKR1C1 and AKR1C4 are responsible for
            sexual development dysgenesis and mutations in AKR1D1 are causative
            in bile-acid deficiency.
            Review article
REFERENCE   6  (bases 1 to 1192)
  AUTHORS   Khanna,M., Qin,K.N., Wang,R.W. and Cheng,K.C.
  TITLE     Substrate specificity, gene structure, and tissue-specific
            distribution of multiple human 3 alpha-hydroxysteroid
            dehydrogenases
  JOURNAL   J Biol Chem 270 (34), 20162-20168 (1995)
   PUBMED   7650035
REFERENCE   7  (bases 1 to 1192)
  AUTHORS   Khanna,M., Qin,K.N. and Cheng,K.C.
  TITLE     Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain
            and molecular cloning of multiple cDNAs encoding structurally
            related proteins in humans
  JOURNAL   J Steroid Biochem Mol Biol 53 (1-6), 41-46 (1995)
   PUBMED   7626489
REFERENCE   8  (bases 1 to 1192)
  AUTHORS   Binstock,J.M., Iyer,R.B., Hamby,C.V., Fried,V.A., Schwartz,I.S.,
            Weinstein,B.I. and Southren,A.L.
  TITLE     Human hepatic 3 alpha-hydroxysteroid dehydrogenase: possible
            identity with human hepatic chlordecone reductase
  JOURNAL   Biochem Biophys Res Commun 187 (2), 760-766 (1992)
   PUBMED   1530633
REFERENCE   9  (bases 1 to 1192)
  AUTHORS   Winters,C.J., Molowa,D.T. and Guzelian,P.S.
  TITLE     Isolation and characterization of cloned cDNAs encoding human liver
            chlordecone reductase
  JOURNAL   Biochemistry 29 (4), 1080-1087 (1990)
   PUBMED   2187532
REFERENCE   10 (bases 1 to 1192)
  AUTHORS   Molowa,D.T., Shayne,A.G. and Guzelian,P.S.
  TITLE     Purification and characterization of chlordecone reductase from
            human liver
  JOURNAL   J Biol Chem 261 (27), 12624-12627 (1986)
   PUBMED   2427522
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL355303.17.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 21, 2020 this sequence version replaced NM_001818.4.
            
            Summary: This gene encodes a member of the aldo/keto reductase
            superfamily, which consists of more than 40 known enzymes and
            proteins. These enzymes catalyze the conversion of aldehydes and
            ketones to their corresponding alcohols by utilizing NADH and/or
            NADPH as cofactors. The enzymes display overlapping but distinct
            substrate specificity. This enzyme catalyzes the bioreduction of
            chlordecone, a toxic organochlorine pesticide, to chlordecone
            alcohol in liver. This gene shares high sequence identity with
            three other gene members and is clustered with those three genes at
            chromosome 10p15-p14. [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC020744.1, D26125.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2144835, SAMEA2145122
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000263126.3/ ENSP00000263126.1
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-115               AL355303.17        55373-55487
            116-283             AL355303.17        58717-58884
            284-400             AL355303.17        62913-63029
            401-478             AL355303.17        64293-64370
            479-601             AL355303.17        64811-64933
            602-711             AL355303.17        71152-71261
            712-877             AL355303.17        71530-71695
            878-960             AL355303.17        75247-75329
            961-1192            AL355303.17        77254-77485
FEATURES             Location/Qualifiers
     source          1..1192
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10p15.1"
     gene            1..1192
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /note="aldo-keto reductase family 1 member C4"
                     /db_xref="GeneID:1109"
                     /db_xref="HGNC:HGNC:387"
                     /db_xref="MIM:600451"
     exon            1..115
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /inference="alignment:Splign:2.1.0"
     CDS             32..1003
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /EC_number="1.1.1.225"
                     /EC_number="1.1.1.62"
                     /EC_number="1.1.1.209"
                     /EC_number="1.1.1.51"
                     /EC_number="1.1.1.357"
                     /EC_number="1.1.1.210"
                     /EC_number="1.1.1.53"
                     /note="dihydrodiol dehydrogenase isozyme DD4; type I
                     3-alpha-hydroxysteroid dehydrogenase; 3-alpha-HSD1;
                     chlordecone reductase; 3-alpha hydroxysteroid
                     dehydrogenase, type I; dihydrodiol dehydrogenase 4;
                     3alpha-hydroxysteroid 3-dehydrogenase"
                     /codon_start=1
                     /product="aldo-keto reductase family 1 member C4"
                     /protein_id="NP_001809.4"
                     /db_xref="CCDS:CCDS7064.1"
                     /db_xref="GeneID:1109"
                     /db_xref="HGNC:HGNC:387"
                     /db_xref="MIM:600451"
                     /translation="MDPKYQRVELNDGHFMPVLGFGTYAPPEVPRNRAVEVTKLAIEA
                     GFRHIDSAYLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCTFFQPQMVQPALESS
                     LKKLQLDYVDLYLLHFPMALKPGETPLPKDENGKVIFDTVDLSATWEVMEKCKDAGLA
                     KSIGVSNFNCRQLEMILNKPGLKYKPVCNQVECHPYLNQSKLLDFCKSKDIVLVAHSA
                     LGTQRHKLWVDPNSPVLLEDPVLCALAKKHKQTPALIALRYQLQRGVVVLAKSYNEQR
                     IRENIQVFEFQLTSEDMKVLDGLNRNYRYVVMDFLMDHPDYPFSDEY"
     exon            116..283
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /inference="alignment:Splign:2.1.0"
     exon            284..400
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /inference="alignment:Splign:2.1.0"
     exon            401..478
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /inference="alignment:Splign:2.1.0"
     exon            479..601
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /inference="alignment:Splign:2.1.0"
     exon            602..711
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /inference="alignment:Splign:2.1.0"
     exon            712..877
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /inference="alignment:Splign:2.1.0"
     exon            878..960
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /inference="alignment:Splign:2.1.0"
     exon            961..1192
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1170..1175
                     /regulatory_class="polyA_signal_sequence"
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /note="hexamer: AATAAA"
     polyA_site      1192
                     /gene="AKR1C4"
                     /gene_synonym="3-alpha-HSD; C11; CDR; CHDR; DD-4; DD4;
                     HAKRA"
                     /note="major polyA site"
ORIGIN      
        1 aggatctgct tagtgaaaga agtggcaagc aatggatccc aaatatcagc gtgtagagct
       61 aaatgatggt cacttcatgc ccgtattggg atttggcacc tatgcacctc cagaggttcc
      121 gaggaacaga gctgtagagg tcaccaaatt agcaatagaa gctggcttcc gccatattga
      181 ttctgcttat ttatacaata atgaggagca ggttggactg gccatccgaa gcaagattgc
      241 agatggcagt gtgaagagag aagacatatt ctacacttca aagctttggt gcactttctt
      301 tcaaccacag atggtccaac cagccttgga aagctcactg aaaaaacttc aactggacta
      361 tgttgacctc tatcttcttc atttcccaat ggctctcaag ccaggtgaga cgccactacc
      421 aaaagatgaa aatggaaaag taatattcga cacagtggat ctctctgcca catgggaggt
      481 catggagaag tgtaaggatg caggattggc caagtccatc ggggtgtcaa acttcaactg
      541 caggcagctg gagatgatcc tcaacaagcc aggactcaag tacaagcctg tctgcaacca
      601 ggtagaatgt catccttacc tcaaccagag caaactgctg gatttctgca agtcaaaaga
      661 cattgttctg gttgcccaca gtgctctggg aacccaacga cataaactat gggtggaccc
      721 aaactcccca gttcttttgg aggacccagt tctttgtgcc ttagcaaaga aacacaaaca
      781 aaccccagcc ctgattgccc tgcgctacca gctgcagcgt ggggttgtgg tcctggccaa
      841 gagctacaat gagcagcgga tcagagagaa catccaggtt tttgaattcc agttgacatc
      901 agaggatatg aaagttctag atggtctaaa cagaaattat cgatatgttg tcatggattt
      961 tcttatggac catcctgatt atccattttc agatgaatat tagcatagag ggtgttgcac
     1021 gacatctagc agaaggccct gtgtgtggat ggtgatgcag aggatgtctc tatgctggtg
     1081 actggacaca cagcctctgg ttaaatccct cccctcctgc ttggcaactt cagctagcta
     1141 gatatatcca tggtccagaa agcaaacata ataaattttt atcttgaagt aa
//
