LOCUS       NM_004483               1560 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens glycine cleavage system protein H (GCSH), transcript
            variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_004483
VERSION     NM_004483.5
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 1560)
  AUTHORS   Arribas-Carreira,L., Dallabona,C., Swanson,M.A., Farris,J.,
            Ostergaard,E., Tsiakas,K., Hempel,M., Aquaviva-Bourdain,C.,
            Koutsoukos,S., Stence,N.V., Magistrati,M., Spector,E.B.,
            Kronquist,K., Christensen,M., Karstensen,H.G., Feichtinger,R.G.,
            Achleitner,M.T., Lawrence Merritt Ii,J., Perez,B., Ugarte,M.,
            Grunewald,S., Riela,A.R., Julve,N., Arnoux,J.B., Haldar,K.,
            Donnini,C., Santer,R., Lund,A.M., Mayr,J.A., Rodriguez-Pombo,P. and
            Van Hove,J.L.K.
  TITLE     Pathogenic variants in GCSH encoding the moonlighting H-protein
            cause combined nonketotic hyperglycinemia and lipoate deficiency
  JOURNAL   Hum Mol Genet 32 (6), 917-933 (2023)
   PUBMED   36190515
  REMARK    GeneRIF: Pathogenic variants in GCSH encoding the moonlighting
            H-protein cause combined nonketotic hyperglycinemia and lipoate
            deficiency.
REFERENCE   2  (bases 1 to 1560)
  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   3  (bases 1 to 1560)
  AUTHORS   Majethia,P., Somashekar,P.H., Hebbar,M., Kadavigere,R.,
            Praveen,B.K., Girisha,K.M. and Shukla,A.
  TITLE     Biallelic start loss variant, c.1A > G in GCSH is associated with
            variant nonketotic hyperglycinemia
  JOURNAL   Clin Genet 100 (2), 201-205 (2021)
   PUBMED   33890291
  REMARK    GeneRIF: Biallelic start loss variant, c.1A > G in GCSH is
            associated with variant nonketotic hyperglycinemia.
REFERENCE   4  (bases 1 to 1560)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   5  (bases 1 to 1560)
  AUTHORS   Adamus,A., Muller,P., Nissen,B., Kasten,A., Timm,S., Bauwe,H.,
            Seitz,G. and Engel,N.
  TITLE     GCSH antisense regulation determines breast cancer cells' viability
  JOURNAL   Sci Rep 8 (1), 15399 (2018)
   PUBMED   30337557
  REMARK    GeneRIF: GCSH protein is overexpressed in both, breast cancer
            tissue and breast cancer cell lines. A shorter (391 bp) transcript
            variant (Tv*) was amplified with an increased expression in healthy
            breast cells and a decreased expression in breast cancer samples. A
            GCSH-equilibrium at the transcript level is likely conceivable for
            optimal glycine degradation.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 1560)
  AUTHORS   Van Hove,J.L.K., Coughlin,C. II, Swanson,M. and Hennermann,J.B.
  TITLE     Nonketotic Hyperglycinemia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301531
REFERENCE   7  (bases 1 to 1560)
  AUTHORS   Fujiwara,K., Okamura-Ikeda,K., Hayasaka,K. and Motokawa,Y.
  TITLE     The primary structure of human H-protein of the glycine cleavage
            system deduced by cDNA cloning
  JOURNAL   Biochem Biophys Res Commun 176 (2), 711-716 (1991)
   PUBMED   2025283
REFERENCE   8  (bases 1 to 1560)
  AUTHORS   Koyata,H. and Hiraga,K.
  TITLE     The glycine cleavage system: structure of a cDNA encoding human
            H-protein, and partial characterization of its gene in patients
            with hyperglycinemias
  JOURNAL   Am J Hum Genet 48 (2), 351-361 (1991)
   PUBMED   1671321
REFERENCE   9  (bases 1 to 1560)
  AUTHORS   Hiraga,K., Kure,S., Yamamoto,M., Ishiguro,Y. and Suzuki,T.
  TITLE     Cloning of cDNA encoding human H-protein, a constituent of the
            glycine cleavage system
  JOURNAL   Biochem Biophys Res Commun 151 (2), 758-762 (1988)
   PUBMED   3348809
REFERENCE   10 (bases 1 to 1560)
  AUTHORS   Grundig,E., Birnbaumer,E. and Hawrylewicz,A.
  TITLE     Influence of phenothiazines or reserpine on the formation of
            14C-glycine from U-14C-serine
  JOURNAL   Enzyme 26 (1), 43-48 (1981)
   PUBMED   6111451
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC092718.3, CN283809.1,
            AV696698.1 and BF798008.1.
            
            On Aug 31, 2019 this sequence version replaced NM_004483.4.
            
            Summary: Degradation of glycine is brought about by the glycine
            cleavage system, which is composed of four mitochondrial protein
            components: P protein (a pyridoxal phosphate-dependent glycine
            decarboxylase), H protein (a lipoic acid-containing protein), T
            protein (a tetrahydrofolate-requiring enzyme), and L protein (a
            lipoamide dehydrogenase). The protein encoded by this gene is the H
            protein, which transfers the methylamine group of glycine from the
            P protein to the T protein. Defects in this gene are a cause of
            nonketotic hyperglycinemia (NKH). Two transcript variants, one
            protein-coding and the other probably not protein-coding,have been
            found for this gene. Also, several transcribed and non-transcribed
            pseudogenes of this gene exist throughout the genome.[provided by
            RefSeq, Jan 2010].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and is the protein-coding variant.
            
            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 :: BC009065.1, M69175.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: inferred from homology
            MANE Ensembl match                 :: ENST00000315467.9/
                                                  ENSP00000319531.3
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-20                AC092718.3         86438-86457
            21-178              CN283809.1         34-191
            179-265             AV696698.1         56-142
            266-541             BF798008.1         117-392
            542-1560            AC092718.3         99870-100888
FEATURES             Location/Qualifiers
     source          1..1560
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q23.2"
     gene            1..1560
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /note="glycine cleavage system protein H"
                     /db_xref="GeneID:2653"
                     /db_xref="HGNC:HGNC:4208"
                     /db_xref="MIM:238330"
     exon            1..265
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /inference="alignment:Splign:2.1.0"
     CDS             118..639
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /note="lipoic acid-containing protein; glycine cleavage
                     system protein H (aminomethyl carrier); mitochondrial
                     glycine cleavage system H-protein"
                     /codon_start=1
                     /product="glycine cleavage system H protein, mitochondrial
                     precursor"
                     /protein_id="NP_004474.2"
                     /db_xref="CCDS:CCDS10933.1"
                     /db_xref="GeneID:2653"
                     /db_xref="HGNC:HGNC:4208"
                     /db_xref="MIM:238330"
                     /translation="MALRVVRSVRALLCTLRAVPSPAAPCPPRPWQLGVGAVRTLRTG
                     PALLSVRKFTEKHEWVTTENGIGTVGISNFAQEALGDVVYCSLPEVGTKLNKQDEFGA
                     LESVKAASELYSPLSGEVTEINEALAENPGLVNKSCYEDGWLIKMTLSNPSELDELMS
                     EEAYEKYIKSIEE"
     exon            266..345
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /inference="alignment:Splign:2.1.0"
     exon            346..409
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /inference="alignment:Splign:2.1.0"
     exon            410..541
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /inference="alignment:Splign:2.1.0"
     exon            542..1560
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1161..1166
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /note="hexamer: AATAAA"
     polyA_site      1184
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /note="major polyA site"
     regulatory      1371..1376
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /note="hexamer: AATAAA"
     polyA_site      1390
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /note="major polyA site"
     regulatory      1522..1527
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
                     /note="hexamer: AATAAA"
     polyA_site      1560
                     /gene="GCSH"
                     /gene_synonym="GCE; MMDS7; NKH"
ORIGIN      
        1 accgcctccg cgcctccatc cagccggctc cctccggccg cgaactgccc ctccccgccc
       61 cgcctcccgg cgcgggtggc cgaggcgtag cgctgcgacc cccgcacccc tgcgaacatg
      121 gcgctgcgag tggtgcggag cgtgcgggcc ctgctctgca ccctgcgcgc ggtcccgtca
      181 cccgccgcgc cctgcccgcc gaggccctgg cagctggggg tgggcgccgt ccgtacgctg
      241 cgcactggac ccgctctgct ctcggtgcgt aaattcacag agaaacacga atgggtaaca
      301 acagaaaatg gcattggaac agtgggaatc agcaattttg cacaggaagc gttgggagat
      361 gttgtttatt gtagtctccc tgaagttggg acaaaattga acaaacaaga tgagtttggt
      421 gctttggaaa gtgtgaaagc tgctagtgaa ctctattctc ctttatcagg agaagtaact
      481 gaaattaatg aagctcttgc agaaaatcca ggacttgtaa acaaatcttg ttatgaagat
      541 ggttggctga tcaagatgac actgagtaac ccttcagaac tagatgaact tatgagtgaa
      601 gaagcatatg agaaatacat aaaatctatt gaggagtgaa aatggaactc ctaaataaac
      661 tagtatgaaa taacgcaagc cagcagagtt gtcttaaatt agtggtggat agaagactta
      721 gaatagaaac ttttagtatt accgatgggg aaaaaaaaac tactgttaac actgctaatg
      781 aaagaaaatg ccctttaact ttctaatgat tatagataaa tataatatgc gtctttttca
      841 caatatccta tgatttttag actaggctct agtgttcaga attcatgaaa ttatccatgg
      901 taaaaactag ttataaaaat tacataattc aaagataaca ttgttattct taagccttat
      961 ataatattgt aacttgcatg tatccatacc tggatttggg atgaaatact taatgatctt
     1021 tccattggaa ataactggaa gtgaagaggt tttgttgctt gtacagtgtc agatgaggaa
     1081 caccactatc ttaattttgc gatacactgc atttgctggt gctattttta tacagtgaag
     1141 caacagcttt gcagcaaaat aataaaatac ttcttcgtta atcatgtttg ttttgatgtt
     1201 aatatttcat ttagtaactc tgctagtatt tgtgaaagtg ctaactttaa cttacggaaa
     1261 gttacttttt aaaaggaaat ttaagccaga acaatgcaaa gctccaagaa aatgttttct
     1321 ttagtcacaa atctggtttt tcttaagcca agatctgtca cctttaacat aataaaaaat
     1381 aaatcaccaa ctttgatttt ctatcatgcg aggtctgaag aaagaagagg aaagacagag
     1441 gaaggtggaa gttttgatca gtatagcaca tggtgttttt aagttgttaa accacgttca
     1501 ggtttccact taagtcatgg gaataaaagt ggacaaggac tgaagcttta tgagctcaga
//
