LOCUS       NM_000161               2916 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens GTP cyclohydrolase 1 (GCH1), transcript variant 1,
            mRNA.
ACCESSION   NM_000161
VERSION     NM_000161.3
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   Tai,F., Zhai,R., Ding,K., Zhang,Y., Yang,H., Li,H., Wang,Q.,
            Cao,Z., Ge,C., Fu,H., Xiao,F. and Zheng,X.
  TITLE     Long non-coding RNA lung cancer-associated transcript 1 regulates
            ferroptosis via microRNA-34a-5p-mediated GTP cyclohydrolase 1
            downregulation in lung cancer cells
  JOURNAL   Int J Oncol 64 (6) (2024)
   PUBMED   38757341
  REMARK    GeneRIF: Long non-coding RNA lung cancer-associated transcript 1
            regulates ferroptosis via microRNA-34a-5p-mediated GTP
            cyclohydrolase 1 downregulation in lung cancer cells.
REFERENCE   2  (bases 1 to 2916)
  AUTHORS   Jung-Klawitter,S., Richter,P., Yuan,Y., Welzel,K., Kube,M.,
            Bahr,S., Leibner,A., Flory,E. and Opladen,T.
  TITLE     Tyrosine hydroxylase variants influence protein expression,
            cellular localization, stability, enzymatic activity and the
            physical interaction between tyrosine hydroxylase and GTP
            cyclohydrolase 1
  JOURNAL   J Inherit Metab Dis 47 (3), 517-532 (2024)
   PUBMED   38084654
  REMARK    GeneRIF: Tyrosine hydroxylase variants influence protein
            expression, cellular localization, stability, enzymatic activity
            and the physical interaction between tyrosine hydroxylase and GTP
            cyclohydrolase 1.
REFERENCE   3  (bases 1 to 2916)
  AUTHORS   Wang,Z., Zhang,N., Zhang,M., Jiang,Y., Ng,A.S., Bridges,E.,
            Zhang,W., Zeng,X., Luo,Q., Liang,J., Gyorffy,B., Hublitz,P.,
            Liang,Z., Fischer,R., Kerr,D., Harris,A.L. and Cai,S.
  TITLE     GTP Cyclohydrolase Drives Breast Cancer Development and Promotes
            EMT in an Enzyme-Independent Manner
  JOURNAL   Cancer Res 83 (20), 3400-3413 (2023)
   PUBMED   37463466
  REMARK    GeneRIF: GTP Cyclohydrolase Drives Breast Cancer Development and
            Promotes EMT in an Enzyme-Independent Manner.
REFERENCE   4  (bases 1 to 2916)
  AUTHORS   Yin,Y.L., Chen,Y., Ren,F., Wang,L., Zhu,M.L., Lu,J.X., Wang,Q.Q.,
            Lu,C.B., Liu,C., Bai,Y.P., Wang,S.X., Wang,J.Z. and Li,P.
  TITLE     Nitrosative stress induced by homocysteine thiolactone drives
            vascular cognitive impairments via GTP cyclohydrolase 1
            S-nitrosylation in vivo
  JOURNAL   Redox Biol 58, 102540 (2022)
   PUBMED   36399957
  REMARK    GeneRIF: Nitrosative stress induced by homocysteine thiolactone
            drives vascular cognitive impairments via GTP cyclohydrolase 1
            S-nitrosylation in vivo.
REFERENCE   5  (bases 1 to 2916)
  AUTHORS   Furukawa,Y.
  TITLE     GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301681
REFERENCE   6  (bases 1 to 2916)
  AUTHORS   Klein,C., Lohmann,K., Marras,C. and Munchau,A.
  TITLE     Hereditary Dystonia Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301334
REFERENCE   7  (bases 1 to 2916)
  AUTHORS   Gutlich,M., Schott,K., Werner,T., Bacher,A. and Ziegler,I.
  TITLE     Species and tissue specificity of mammalian GTP cyclohydrolase I
            messenger RNA
  JOURNAL   Biochim Biophys Acta 1171 (2), 133-140 (1992)
   PUBMED   1482676
REFERENCE   8  (bases 1 to 2916)
  AUTHORS   Togari,A., Ichinose,H., Matsumoto,S., Fujita,K. and Nagatsu,T.
  TITLE     Multiple mRNA forms of human GTP cyclohydrolase I
  JOURNAL   Biochem Biophys Res Commun 187 (1), 359-365 (1992)
   PUBMED   1520321
REFERENCE   9  (bases 1 to 2916)
  AUTHORS   .
  TITLE     Argentinian corned beef
  JOURNAL   CDR (Lond Engl Wkly) 1 (24), 107 (1991)
   PUBMED   1669853
REFERENCE   10 (bases 1 to 2916)
  AUTHORS   Schoedon,G., Redweik,U. and Curtius,H.C.
  TITLE     Purification of GTP cyclohydrolase I from human liver and
            production of specific monoclonal antibodies
  JOURNAL   Eur J Biochem 178 (3), 627-634 (1989)
   PUBMED   2463916
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL160471.5 and AL133444.4.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000161.2.
            
            Summary: This gene encodes a member of the GTP cyclohydrolase
            family. The encoded protein is the first and rate-limiting enzyme
            in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the
            conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an
            essential cofactor required by aromatic amino acid hydroxylases as
            well as nitric oxide synthases. Mutations in this gene are
            associated with malignant hyperphenylalaninemia and dopa-responsive
            dystonia. Several alternatively spliced transcript variants
            encoding different isoforms have been described; however, not all
            variants give rise to a functional enzyme. [provided by RefSeq, Jul
            2008].
            
            Transcript Variant: This variant (1), also known as Type I,
            represents the longest transcript. Variants 1 and 2 encode the
            longest isoform (1), which is the active enzyme.
            
            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 :: BC025415.2, U66097.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000491895.7/ ENSP00000419045.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-506               AL160471.5         131109-131614
            507-616             AL160471.5         168499-168608
            617-672             AL160471.5         174199-174254
            673-704             AL160471.5         186805-186836
            705-789             AL160471.5         188083-188167
            790-2556            AL160471.5         189792-191558
            2557-2916           AL133444.4         190841-191200       c
FEATURES             Location/Qualifiers
     source          1..2916
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q22.2"
     gene            1..2916
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /note="GTP cyclohydrolase 1"
                     /db_xref="GeneID:2643"
                     /db_xref="HGNC:HGNC:4193"
                     /db_xref="MIM:600225"
     exon            1..506
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /inference="alignment:Splign:2.1.0"
     CDS             164..916
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /EC_number="3.5.4.16"
                     /note="isoform 1 is encoded by transcript variant 1;
                     dystonia 14; guanosine 5'-triphosphate cyclohydrolase I;
                     GTP-CH-I; GTP cyclohydrolase I"
                     /codon_start=1
                     /product="GTP cyclohydrolase 1 isoform 1"
                     /protein_id="NP_000152.1"
                     /db_xref="CCDS:CCDS9720.1"
                     /db_xref="GeneID:2643"
                     /db_xref="HGNC:HGNC:4193"
                     /db_xref="MIM:600225"
                     /translation="MEKGPVRAPAEKPRGARCSNGFPERDPPRPGPSRPAEKPPRPEA
                     KSAQPADGWKGERPRSEEDNELNLPNLAAAYSSILSSLGENPQRQGLLKTPWRAASAM
                     QFFTKGYQETISDVLNDAIFDEDHDEMVIVKDIDMFSMCEHHLVPFVGKVHIGYLPNK
                     QVLGLSKLARIVEIYSRRLQVQERLTKQIAVAITEALRPAGVGVVVEATHMCMVMRGV
                     QKMNSKTVTSTMLGVFREDPKTREEFLTLIRS"
     exon            507..616
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /inference="alignment:Splign:2.1.0"
     exon            617..672
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /inference="alignment:Splign:2.1.0"
     exon            673..704
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /inference="alignment:Splign:2.1.0"
     exon            705..789
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /inference="alignment:Splign:2.1.0"
     exon            790..2916
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2898..2903
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /note="hexamer: ATTAAA"
     polyA_site      2916
                     /gene="GCH1"
                     /gene_synonym="DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1;
                     HPABH4B"
                     /note="major polyA site"
ORIGIN      
        1 agcctgtggc cgctcccggc tcggagtgtg atctaagcag gttgcgtacc ttcctcaggt
       61 gactccggcc acagcccatt gtccgcggcc accggcggag tttagccgca gacctcgaag
      121 cgccccgggg tccttcccga acggcagcgg ctgcggcggg tccatggaga agggccctgt
      181 gcgggcaccg gcggagaagc cgcggggcgc caggtgcagc aatgggttcc ccgagcggga
      241 tccgccgcgg cccgggccca gcaggccggc ggagaagccc ccgcggcccg aggccaagag
      301 cgcgcagccc gcggacggct ggaagggcga gcggccccgc agcgaggagg ataacgagct
      361 gaacctccct aacctggcag ccgcctactc gtccatcctg agctcgctgg gcgagaaccc
      421 ccagcggcaa gggctgctca agacgccctg gagggcggcc tcggccatgc agttcttcac
      481 caagggctac caggagacca tctcagatgt cctaaacgat gctatatttg atgaagatca
      541 tgatgagatg gtgattgtga aggacataga catgttttcc atgtgtgagc atcacttggt
      601 tccatttgtt ggaaaggtcc atattggtta tcttcctaac aagcaagtcc ttggcctcag
      661 caaacttgcg aggattgtag aaatctatag tagaagacta caagttcagg agcgccttac
      721 aaaacaaatt gctgtagcaa tcacggaagc cttgcggcct gctggagtcg gggtagtggt
      781 tgaagcaaca cacatgtgta tggtaatgcg aggtgtacag aaaatgaaca gcaaaactgt
      841 gaccagcaca atgttgggtg tgttccggga ggatccaaag actcgggaag agttcctgac
      901 tctcattagg agctgagctt cattcagtgt gtgtgcgttg gttgccgatc gtactgccag
      961 tagcattgtc tgtctgtccg gtcttgtttg tacattccat tttcaattgt tacagatgtg
     1021 aactttattc cttgtcacta attatattta aaattatttc taggaagtca aataaatata
     1081 ataaagggtt gagccctcta ctttcttctt gccacctttt tgtggcaata ttaaagtgaa
     1141 ctgctaatag tgtaagtacg tgcacaaaac cactgccaga taaccagagg ggcctgggaa
     1201 gggagaagaa ttagtgtatt tttttcaaat agtacagtaa tttgcctcat aagcatagga
     1261 gcattgggaa tgagagggaa ctgtgcccag tatactgttt tttttcttcc tccaataaaa
     1321 gtggtgtagt gccgaaagtg ctaaaatatt tagtgcggta ttgctctgtg aattcaagtt
     1381 caacagactt cactttggtc atgtttatta aaccaccagt gacatttaaa aatatatttt
     1441 tagcagtcgt aatgttagtc accaagggaa ggtggtggaa tgtctatgtt tttgatttta
     1501 ctgtgagtta aaaaggcaca tttctacctt ctattgtttt taaattcaag aatagggaat
     1561 tagttcctgg tgttgtttac gagtgtattc tcgtgtcaac atacagggat ttagacattt
     1621 aactctctgt gccttgataa gaatatcatt tagagtgtag atacttttgc ctttttaaaa
     1681 aagccattat tttatgagac ttagtactca cactgcaaat aactagtcag ctcagtttta
     1741 actttatagg tttattgagt ttcctttgtg tgatccatgt agatgcctca aaatgtttct
     1801 tcttcttctt ttttttaatc ttataagata tttttctaag tatttccaga aacatttgag
     1861 agtgcccatc attttcaggt ctgcagaacc atagcttcca cgcacctgaa cgagcacaga
     1921 atgaactgac ggtggaagac attatgagct gtgtccaacg ttttaaccaa agcgtatcgt
     1981 accaacgatc tgtgaaaatg cactggaagc ttctggtccc ggtttccttt gtggtctatg
     2041 tgggtcttgt cctcattgta actccgtata gatggtatag gtattttaat cctggaagct
     2101 gttgccttat taatgattat cttaaaattt cctccattgg ggcagcgtgg gccaaattaa
     2161 aacaaacaaa accgcaactc ctccacagaa acacaaacac agttattcca tgaagtttag
     2221 tatttggttg acatagtgct cttcaaattc atcccattac cctaaaagta ataactttga
     2281 tgcttgcttt aactttagtc ccatctctgc cactttgatg ctatttgggt tatgatgggg
     2341 caagatggca gaggtattgg gtttttttgt ttttttccat tcctctctac ttctgtttcc
     2401 tagctttttc tttctggagt ttaagtacag tgatggttgg cttgagtacc tttttaaatc
     2461 tagcccagta taaacattag cctgcttaat atttagacat ttataggtag aattctgagc
     2521 actcaactca tgtttggcat tttaaagtaa aaacaagtgt gacttcgagg accaaagaaa
     2581 ttgtcagcta tacatttatc tttatgaact catttatatt cctttttaat gactcgttgt
     2641 tctaacattt cctagaagtg ttcttataaa ggtctaatgt atccacaggc tgttgtctta
     2701 ttagtaaatg caaagtaatg actttgtctg ttttactcta gtctttagta cttcaaaatt
     2761 accttttcat atccatgatc ttgagtccat ttgggggatt tttaagaatt tgatgtattt
     2821 caatacactg ttcaaaatta aattgtttaa ttttatgtat gagtatgtat gttcctgaag
     2881 gtggtcctat ttaaattatt aaactattgt aacttt
//
