LOCUS       NM_002495                669 bp    mRNA    linear   PRI 04-OCT-2024
DEFINITION  Homo sapiens NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_002495
VERSION     NM_002495.4
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 669)
  AUTHORS   Sonsalla,G., Malpartida,A.B., Riedemann,T., Gusic,M., Rusha,E.,
            Bulli,G., Najas,S., Janjic,A., Hersbach,B.A., Smialowski,P.,
            Drukker,M., Enard,W., Prehn,J.H.M., Prokisch,H., Gotz,M. and
            Masserdotti,G.
  TITLE     Direct neuronal reprogramming of NDUFS4 patient cells identifies
            the unfolded protein response as a novel general reprogramming
            hurdle
  JOURNAL   Neuron 112 (7), 1117-1132 (2024)
   PUBMED   38266647
  REMARK    GeneRIF: Direct neuronal reprogramming of NDUFS4 patient cells
            identifies the unfolded protein response as a novel general
            reprogramming hurdle.
REFERENCE   2  (bases 1 to 669)
  AUTHORS   van de Wal,M.A.E., Adjobo-Hermans,M.J.W., Keijer,J.,
            Schirris,T.J.J., Homberg,J.R., Wieckowski,M.R., Grefte,S., van
            Schothorst,E.M., van Karnebeek,C., Quintana,A. and Koopman,W.J.H.
  TITLE     Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and
            intervention
  JOURNAL   Brain 145 (1), 45-63 (2022)
   PUBMED   34849584
  REMARK    GeneRIF: Ndufs4 knockout mouse models of Leigh syndrome:
            pathophysiology and intervention.
            Review article
REFERENCE   3  (bases 1 to 669)
  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   4  (bases 1 to 669)
  AUTHORS   Gonzalez-Quintana,A., Trujillo-Tiebas,M.J., Fernandez-Perrone,A.L.,
            Blazquez,A., Lucia,A., Moran,M., Ugalde,C., Arenas,J., Ayuso,C. and
            Martin,M.A.
  TITLE     Uniparental isodisomy as a cause of mitochondrial complex I
            respiratory chain disorder due to a novel splicing NDUFS4 mutation
  JOURNAL   Mol Genet Metab 131 (3), 341-348 (2020)
   PUBMED   33093004
  REMARK    GeneRIF: Uniparental isodisomy as a cause of mitochondrial complex
            I respiratory chain disorder due to a novel splicing NDUFS4
            mutation.
REFERENCE   5  (bases 1 to 669)
  AUTHORS   Adjobo-Hermans,M.J.W., de Haas,R., Willems,P.H.G.M., Wojtala,A.,
            van Emst-de Vries,S.E., Wagenaars,J.A., van den Brand,M.,
            Rodenburg,R.J., Smeitink,J.A.M., Nijtmans,L.G., Sazanov,L.A.,
            Wieckowski,M.R. and Koopman,W.J.H.
  TITLE     NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4-/- mice and
            Leigh syndrome patients: A stabilizing role for NDUFAF2
  JOURNAL   Biochim Biophys Acta Bioenerg 1861 (8), 148213 (2020)
   PUBMED   32335026
  REMARK    GeneRIF: NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4(-/-)
            mice and Leigh syndrome patients: A stabilizing role for NDUFAF2.
REFERENCE   6  (bases 1 to 669)
  AUTHORS   Loeffen,J.L., Triepels,R.H., van den Heuvel,L.P., Schuelke,M.,
            Buskens,C.A., Smeets,R.J., Trijbels,J.M. and Smeitink,J.A.
  TITLE     cDNA of eight nuclear encoded subunits of NADH:ubiquinone
            oxidoreductase: human complex I cDNA characterization completed
  JOURNAL   Biochem Biophys Res Commun 253 (2), 415-422 (1998)
   PUBMED   9878551
REFERENCE   7  (bases 1 to 669)
  AUTHORS   van den Heuvel,L., Ruitenbeek,W., Smeets,R., Gelman-Kohan,Z.,
            Elpeleg,O., Loeffen,J., Trijbels,F., Mariman,E., de Bruijn,D. and
            Smeitink,J.
  TITLE     Demonstration of a new pathogenic mutation in human complex I
            deficiency: a 5-bp duplication in the nuclear gene encoding the
            18-kD (AQDQ) subunit
  JOURNAL   Am J Hum Genet 62 (2), 262-268 (1998)
   PUBMED   9463323
REFERENCE   8  (bases 1 to 669)
  AUTHORS   Emahazion,T., Beskow,A., Gyllensten,U. and Brookes,A.J.
  TITLE     Intron based radiation hybrid mapping of 15 complex I genes of the
            human electron transport chain
  JOURNAL   Cytogenet Cell Genet 82 (1-2), 115-119 (1998)
   PUBMED   9763677
REFERENCE   9  (bases 1 to 669)
  AUTHORS   Rahman,S. and Thorburn,D.
  TITLE     Nuclear Gene-Encoded Leigh Syndrome Spectrum Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   26425749
REFERENCE   10 (bases 1 to 669)
  AUTHORS   Pilkington,S.J., Skehel,J.M., Gennis,R.B. and Walker,J.E.
  TITLE     Relationship between mitochondrial NADH-ubiquinone reductase and a
            bacterial NAD-reducing hydrogenase
  JOURNAL   Biochemistry 30 (8), 2166-2175 (1991)
   PUBMED   1900194
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CD692133.1, BU954271.1 and
            AI001139.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_002495.3.
            
            Summary: This gene encodes an nuclear-encoded accessory subunit of
            the mitochondrial membrane respiratory chain NADH dehydrogenase
            (complex I, or NADH:ubiquinone oxidoreductase). Complex I removes
            electrons from NADH and passes them to the electron acceptor
            ubiquinone. Mutations in this gene can cause mitochondrial complex
            I deficiencies such as Leigh syndrome. Alternative splicing results
            in multiple transcript variants. [provided by RefSeq, Dec 2015].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            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 :: SRR5189652.228584.1,
                                           SRR5189655.5102.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000296684.10/
                                                  ENSP00000296684.5
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-5                 CD692133.1         23-27
            6-662               BU954271.1         4-660
            663-669             AI001139.1         4-10                c
FEATURES             Location/Qualifiers
     source          1..669
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q11.2"
     gene            1..669
                     /gene="NDUFS4"
                     /gene_synonym="AQDQ; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1"
                     /note="NADH:ubiquinone oxidoreductase subunit S4"
                     /db_xref="GeneID:4724"
                     /db_xref="HGNC:HGNC:7711"
                     /db_xref="MIM:602694"
     exon            1..122
                     /gene="NDUFS4"
                     /gene_synonym="AQDQ; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1"
                     /inference="alignment:Splign:2.1.0"
     CDS             25..552
                     /gene="NDUFS4"
                     /gene_synonym="AQDQ; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; complex I 18kDa subunit; NADH dehydrogenase
                     [ubiquinone] iron-sulfur protein 4, mitochondrial;
                     NADH-ubiquinone oxidoreductase 18 kDa subunit;
                     mitochondrial respiratory chain complex I (18-KD subunit);
                     complex I-AQDQ; NADH dehydrogenase (ubiquinone) Fe-S
                     protein 4, 18kDa (NADH-coenzyme Q reductase)"
                     /codon_start=1
                     /product="NADH dehydrogenase [ubiquinone] iron-sulfur
                     protein 4, mitochondrial isoform 1 precursor"
                     /protein_id="NP_002486.1"
                     /db_xref="CCDS:CCDS3960.1"
                     /db_xref="GeneID:4724"
                     /db_xref="HGNC:HGNC:7711"
                     /db_xref="MIM:602694"
                     /translation="MAAVSMSVVLRQTLWRRRAVAVAALSVSRVPTRSLRTSTWRLAQ
                     DQTQDTQLITVDEKLDITTLTGVPEEHIKTRKVRIFVPARNNMQSGVNNTKKWKMEFD
                     TRERWENPLMGWASTADPLSNMVLTFSTKEDAVSFAEKNGWSYDIEERKVPKPKSKSY
                     GANFSWNKRTRVSTK"
     exon            123..201
                     /gene="NDUFS4"
                     /gene_synonym="AQDQ; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1"
                     /inference="alignment:Splign:2.1.0"
     exon            202..374
                     /gene="NDUFS4"
                     /gene_synonym="AQDQ; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1"
                     /inference="alignment:Splign:2.1.0"
     exon            375..448
                     /gene="NDUFS4"
                     /gene_synonym="AQDQ; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1"
                     /inference="alignment:Splign:2.1.0"
     exon            449..669
                     /gene="NDUFS4"
                     /gene_synonym="AQDQ; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      646..651
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NDUFS4"
                     /gene_synonym="AQDQ; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1"
                     /note="hexamer: AATAAA"
     polyA_site      669
                     /gene="NDUFS4"
                     /gene_synonym="AQDQ; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1"
                     /note="major polyA site"
ORIGIN      
        1 atcctggcgt ttgcctgcag caagatggcg gcggtgtcaa tgtcagtggt actgaggcag
       61 acgttgtggc ggagaagggc agtggctgta gctgcccttt ccgtttccag ggttccgacc
      121 aggtcgttga ggacttccac atggagattg gcacaggacc agactcaaga cacacaactc
      181 ataacagttg atgaaaaatt ggatatcact actttaactg gagttccaga agagcatata
      241 aaaactagaa aagtcaggat ctttgttcct gctcgcaata acatgcagtc tggagtaaac
      301 aacacaaaga aatggaagat ggagtttgat accagagagc gatgggaaaa tcctttgatg
      361 ggttgggcat caacggctga tcccttatcc aacatggttc taaccttcag tactaaagaa
      421 gatgcagttt cctttgcaga aaaaaatgga tggagctatg acattgaaga gaggaaggtt
      481 ccaaaaccca agtccaagtc ttatggtgca aacttttctt ggaacaaaag aacaagagta
      541 tccacaaaat aggttggcac tgactatatc tctgcttgac tgtgaataaa gtcagctgtg
      601 cagtatttat agtccatgta taataaatac atctcttaat ctcctaataa attggacctt
      661 taaactaca
//
