LOCUS       NM_000398               2916 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens cytochrome b5 reductase 3 (CYB5R3), transcript variant
            1, mRNA.
ACCESSION   NM_000398 NM_001031678
VERSION     NM_000398.7
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 2916)
  AUTHORS   Chaudhary,R., Straub,A.C., Aggor,F.E.Y., Onasanya,I.,
            Richardson,J., Strollo,P.J., Reis,S.E. and Olafiranye,O.
  TITLE     CYB5R3 T117S Genetic Mutation Is Associated With Major Adverse
            Cardiovascular and Cerebrovascular Events in Black Adults
  JOURNAL   Circ Genom Precis Med 17 (2), e004271 (2024)
   PUBMED   38353123
  REMARK    GeneRIF: CYB5R3 T117S Genetic Mutation Is Associated With Major
            Adverse Cardiovascular and Cerebrovascular Events in Black Adults.
REFERENCE   2  (bases 1 to 2916)
  AUTHORS   Ishimura,R., El-Gowily,A.H., Noshiro,D., Komatsu-Hirota,S., Ono,Y.,
            Shindo,M., Hatta,T., Abe,M., Uemura,T., Lee-Okada,H.C.,
            Mohamed,T.M., Yokomizo,T., Ueno,T., Sakimura,K., Natsume,T.,
            Sorimachi,H., Inada,T., Waguri,S., Noda,N.N. and Komatsu,M.
  TITLE     The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3
  JOURNAL   Nat Commun 13 (1), 7857 (2022)
   PUBMED   36543799
  REMARK    Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2916)
  AUTHORS   Cho,N.H., Cheveralls,K.C., Brunner,A.D., Kim,K., Michaelis,A.C.,
            Raghavan,P., Kobayashi,H., Savy,L., Li,J.Y., Canaj,H., Kim,J.Y.S.,
            Stewart,E.M., Gnann,C., McCarthy,F., Cabrera,J.P., Brunetti,R.M.,
            Chhun,B.B., Dingle,G., Hein,M.Y., Huang,B., Mehta,S.B.,
            Weissman,J.S., Gomez-Sjoberg,R., Itzhak,D.N., Royer,L.A., Mann,M.
            and Leonetti,M.D.
  TITLE     OpenCell: Endogenous tagging for the cartography of human cellular
            organization
  JOURNAL   Science 375 (6585), eabi6983 (2022)
   PUBMED   35271311
REFERENCE   4  (bases 1 to 2916)
  AUTHORS   Deorukhkar,A., Kulkarni,A. and Kedar,P.
  TITLE     Three novel mutations in CYB5R3 gene causing NADH-cytochrome b5
            reductase enzyme deficiency leads to recessive congenital
            methaemoglobinemia
  JOURNAL   Mol Biol Rep 49 (3), 2141-2147 (2022)
   PUBMED   35064402
  REMARK    GeneRIF: Three novel mutations in CYB5R3 gene causing
            NADH-cytochrome b5 reductase enzyme deficiency leads to recessive
            congenital methaemoglobinemia.
REFERENCE   5  (bases 1 to 2916)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   6  (bases 1 to 2916)
  AUTHORS   Shirabe,K., Yubisui,T., Borgese,N., Tang,C.Y., Hultquist,D.E. and
            Takeshita,M.
  TITLE     Enzymatic instability of NADH-cytochrome b5 reductase as a cause of
            hereditary methemoglobinemia type I (red cell type)
  JOURNAL   J Biol Chem 267 (28), 20416-20421 (1992)
   PUBMED   1400360
REFERENCE   7  (bases 1 to 2916)
  AUTHORS   Malkinson,A.M., Siegel,D., Forrest,G.L., Gazdar,A.F., Oie,H.K.,
            Chan,D.C., Bunn,P.A., Mabry,M., Dykes,D.J., Harrison,S.D. et al.
  TITLE     Elevated DT-diaphorase activity and messenger RNA content in human
            non-small cell lung carcinoma: relationship to the response of lung
            tumor xenografts to mitomycin Cl
  JOURNAL   Cancer Res 52 (17), 4752-4757 (1992)
   PUBMED   1324793
REFERENCE   8  (bases 1 to 2916)
  AUTHORS   Narahara,K., Takahashi,Y., Murakami,M., Tsuji,K., Yokoyama,Y.,
            Murakami,R., Ninomiya,S. and Seino,Y.
  TITLE     Terminal 22q deletion associated with a partial deficiency of
            arylsulphatase A
  JOURNAL   J Med Genet 29 (6), 432-433 (1992)
   PUBMED   1352356
  REMARK    Review article
REFERENCE   9  (bases 1 to 2916)
  AUTHORS   Katsube,T., Sakamoto,N., Kobayashi,Y., Seki,R., Hirano,M.,
            Tanishima,K., Tomoda,A., Takazakura,E., Yubisui,T., Takeshita,M. et
            al.
  TITLE     Exonic point mutations in NADH-cytochrome B5 reductase genes of
            homozygotes for hereditary methemoglobinemia, types I and III:
            putative mechanisms of tissue-dependent enzyme deficiency
  JOURNAL   Am J Hum Genet 48 (4), 799-808 (1991)
   PUBMED   1707593
REFERENCE   10 (bases 1 to 2916)
  AUTHORS   Dailey,H.A. and Strittmatter,P.
  TITLE     Modification and identification of cytochrome b5 carboxyl groups
            involved in protein-protein interaction with cytochrome b5
            reductase
  JOURNAL   J Biol Chem 254 (12), 5388-5396 (1979)
   PUBMED   221468
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BX334220.2, BC004821.1 and
            Z93241.11.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000398.6.
            
            Summary: This gene encodes cytochrome b5 reductase, which includes
            a membrane-bound form in somatic cells (anchored in the endoplasmic
            reticulum, mitochondrial and other membranes) and a soluble form in
            erythrocytes. The membrane-bound form exists mainly on the
            cytoplasmic side of the endoplasmic reticulum and functions in
            desaturation and elongation of fatty acids, in cholesterol
            biosynthesis, and in drug metabolism. The erythrocyte form is
            located in a soluble fraction of circulating erythrocytes and is
            involved in methemoglobin reduction. The membrane-bound form has
            both membrane-binding and catalytic domains, while the soluble form
            has only the catalytic domain. Alternate splicing results in
            multiple transcript variants. Mutations in this gene cause
            methemoglobinemias. [provided by RefSeq, Jan 2010].
            
            Transcript Variant: This variant (1) encodes the membrane-bound
            form (isoform 1) of the enzyme. This isoform (1) is referred to in
            the literature as isoform m.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: SRR1660805.151933.1,
                                           SRR1660805.6405.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2142680, SAMEA2148093
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000352397.10/ ENSP00000338461.6
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-49                BX334220.2         8-56
            50-1943             BC004821.1         1-1894
            1944-2916           Z93241.11          79237-80209         c
FEATURES             Location/Qualifiers
     source          1..2916
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q13.2"
     gene            1..2916
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /note="cytochrome b5 reductase 3"
                     /db_xref="GeneID:1727"
                     /db_xref="HGNC:HGNC:2873"
                     /db_xref="MIM:613213"
     exon            1..98
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /inference="alignment:Splign:2.1.0"
     CDS             78..983
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /EC_number="1.6.2.2"
                     /note="isoform 1 is encoded by transcript variant 1;
                     diaphorase-1; NADH-cytochrome b5 reductase 3
                     membrane-bound form; NADH-cytochrome b5 reductase 3
                     soluble form; mutant NADH-cytochrome b5 reductase"
                     /codon_start=1
                     /product="NADH-cytochrome b5 reductase 3 isoform 1"
                     /protein_id="NP_000389.1"
                     /db_xref="CCDS:CCDS33658.1"
                     /db_xref="GeneID:1727"
                     /db_xref="HGNC:HGNC:2873"
                     /db_xref="MIM:613213"
                     /translation="MGAQLSTLGHMVLFPVWFLYSLLMKLFQRSTPAITLESPDIKYP
                     LRLIDREIISHDTRRFRFALPSPQHILGLPVGQHIYLSARIDGNLVVRPYTPISSDDD
                     KGFVDLVIKVYFKDTHPKFPAGGKMSQYLESMQIGDTIEFRGPSGLLVYQGKGKFAIR
                     PDKKSNPIIRTVKSVGMIAGGTGITPMLQVIRAIMKDPDDHTVCHLLFANQTEKDILL
                     RPELEELRNKHSARFKLWYTLDRAPEAWDYGQGFVNEEMIRDHLPPPEEEPLVLMCGP
                     PPMIQYACLPNLDHVGHPTERCFVF"
     exon            99..230
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /inference="alignment:Splign:2.1.0"
     exon            231..303
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /inference="alignment:Splign:2.1.0"
     exon            304..410
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /inference="alignment:Splign:2.1.0"
     exon            411..540
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /inference="alignment:Splign:2.1.0"
     exon            541..624
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /inference="alignment:Splign:2.1.0"
     exon            625..710
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /inference="alignment:Splign:2.1.0"
     exon            711..810
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /inference="alignment:Splign:2.1.0"
     exon            811..2916
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1922..1927
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /note="hexamer: AGTAAA"
     polyA_site      1943
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /note="major polyA site"
     regulatory      2897..2902
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
                     /note="hexamer: AATAAA"
     polyA_site      2916
                     /gene="CYB5R3"
                     /gene_synonym="B5R; DIA1"
ORIGIN      
        1 ggagtgacgc gggcccgggc gcgacggtct cggcggcggc ggcggcggcg acagagcgag
       61 cgcggcgcgg ggccaccatg ggggcccagc tcagcacgtt gggccatatg gtgctcttcc
      121 cagtctggtt cctgtacagt ctgctcatga agctgttcca gcgctccacg ccagccatca
      181 ccctcgagag cccggacatc aagtacccgc tgcggctcat cgaccgggag atcatcagcc
      241 atgacacccg gcgcttccgc tttgccctgc cgtcacccca gcacatcctg ggcctccctg
      301 tcggccagca catctacctc tcggctcgaa ttgatggaaa cctggtcgtc cggccctata
      361 cacccatctc cagcgatgat gacaagggct tcgtggacct ggtcatcaag gtttacttca
      421 aggacaccca tcccaagttt cccgctggag ggaagatgtc tcagtacctg gagagcatgc
      481 agattggaga caccattgag ttccggggcc ccagtgggct gctggtctac cagggcaaag
      541 ggaagttcgc catccgacct gacaaaaagt ccaaccctat catcaggaca gtgaagtctg
      601 tgggcatgat cgcgggaggg acaggcatca ccccgatgct gcaggtgatc cgcgccatca
      661 tgaaggaccc tgatgaccac actgtgtgcc acctgctctt tgccaaccag accgagaagg
      721 acatcctgct gcgacctgag ctggaggaac tcaggaacaa acattctgca cgcttcaagc
      781 tctggtacac gctggacaga gcccctgaag cctgggacta cggccagggc ttcgtgaatg
      841 aggagatgat ccgggaccac cttccacccc cagaggagga gccgctggtg ctgatgtgtg
      901 gccccccacc catgatccag tacgcctgcc ttcccaacct ggaccacgtg ggccacccca
      961 cggagcgctg cttcgtcttc tgagggccgg gcacggtcac acggccaccc gccccgcgca
     1021 ccccacgccc tgttcacgct cacccagtca cctccccaca tcgcacactg gggccccggg
     1081 ttcagcctgg cctgcccgtg ccctggtgaa tcacctggct gagcagttcc cctggagccc
     1141 cttcgggagc agggctgtgt cccagatggg ccacggctga gccttcagag tacgtcctgc
     1201 ctggcactta ctggtcctta ccagagacgc ccagccccat ccctgtcctc atgacccctc
     1261 gtccaccccc cacacacact ataaggctga gggctgccag cagccccgtc tgcccaccat
     1321 tcccggccgt ggaccatagt cgggatgtca gcagacacac atgggcagcc caaagctgca
     1381 ggtgccaggg cccaccccag cctcgcctgt cacccccact cccgcctcag ggccaggccc
     1441 aggcctcacc acctgacgct gcatgagaca ttgacaccag aaagccctct tgggggcact
     1501 gctccctacc ccagggccct ggccagccgg gagcttggct ctcctctggc tagagtggga
     1561 agagggggct ggccatgggg ccctcccaga acctcagcat ttccttccag cccatccaaa
     1621 cactgaggca gccttgggga accccgagct ggggggttgg cagcccactg caccgcctca
     1681 gggttttggg gtcctgggct ggggccacca tccctgatgg cagaactccc acaaccacat
     1741 gtatttattc ctctgtccta aaccgtcccc tccttccctc acccccagca cagggggatt
     1801 ctgagcagtg cctcttgtct gagggacata tcagtgacct cgacgttgcc tttagactac
     1861 agttgtgtta gcctcttgcg tattggcttt ttcagagtca tttatgagca gaaaaaaaaa
     1921 aagtaaaact ttgctaatat taacccttct ctagctcctc gagggtctgt gacctgcaac
     1981 acaaggggtg gggtcaggaa agggctgggg aagacctagc attttttttt tctttttttt
     2041 ttttttttga gacggagtct ccctttgtca cccaggctgg agtggcatga tctcagctca
     2101 ctacaacctc cacctctcgg gttcaagcga ttctcctgcc tcagcctccc gagtagctgg
     2161 gactaaaagt gcccaccacc acacccagct agtttttgta tttttttttt tttttttttg
     2221 agacggagtc tcgctctgtc gcccaggctg gagtgcagtg gcgggatctc ggctcactgc
     2281 aagctccgcc tcccgggttc acgccattct cctgcctcag cctcccaagt agctgggact
     2341 acaggcgccc gccactacgc ccggctaatt ttttgtattt ttagtagaga cggggtttca
     2401 ccgttttagc cgggatggtc tcgatctcct gacctcgtga tccgcccgcc tcggcctccc
     2461 aaagtgctgg gattacaggc gtgagccact gcgcccggct ccagcattta tttctgatgt
     2521 atctttgtgg tagaaaattt ggaaagtgca gagaagtata cacaggaaga aaaattccca
     2581 acccccagag gcaaaccagc tgaaaccacg caaccccagt caccccaatg caccgcgagg
     2641 ctgctgcctc ctgtcagggt cagatgagcc tcgaggctca ggaaagtcag aggatgccat
     2701 ctgcatggtg gtaaattaca gaggtgatga ggcaaggtgg gtgtggggct gttcttaaaa
     2761 cggggcagca ggaaggcccc aaggagatgg atttgggctg ggacgggaag agagagctgg
     2821 ccatgctggg gtgggtgggt gttcaaatgg tggaaacagc agacgcaaag gccctgccgt
     2881 tggaaccagc ttgtggaata aactttcaga aacaga
//
