LOCUS       NM_000375               1336 bp    mRNA    linear   PRI 04-OCT-2024
DEFINITION  Homo sapiens uroporphyrinogen III synthase (UROS), transcript
            variant 2, mRNA.
ACCESSION   NM_000375
VERSION     NM_000375.3
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 1336)
  AUTHORS   Weiss,Y., Balwani,M., Chen,B., Yasuda,M., Nazarenko,I. and
            Desnick,R.J.
  TITLE     Congenital erythropoietic porphyria and erythropoietic
            protoporphyria: Identification of 7 uroporphyrinogen III synthase
            and 20 ferrochelatase novel mutations
  JOURNAL   Mol Genet Metab 128 (3), 358-362 (2019)
   PUBMED   30454868
  REMARK    GeneRIF: These results expand the molecular heterogeneity of the
            erythropoietic porphyrias by adding a total of 7 novel mutations in
            uroporphyrinogen III synthase.
REFERENCE   2  (bases 1 to 1336)
  AUTHORS   Blouin,J.M., Bernardo-Seisdedos,G., Sasso,E., Esteve,J., Ged,C.,
            Lalanne,M., Sanz-Parra,A., Urquiza,P., de Verneuil,H., Millet,O.
            and Richard,E.
  TITLE     Missense UROS mutations causing congenital erythropoietic porphyria
            reduce UROS homeostasis that can be rescued by proteasome
            inhibition
  JOURNAL   Hum Mol Genet 26 (8), 1565-1576 (2017)
   PUBMED   28334762
  REMARK    GeneRIF: we show evidence that abnormal protein homeostasis is a
            prevalent mechanism responsible for UROS deficiency and that
            modulators of UROS proteolysis such as proteasome inhibitors or
            chemical chaperones may represent an attractive therapeutic option
            to reduce porphyrin accumulation and prevent skin photosensitivity
            in Congenital erythropoietic porphyria (CEP)patients when the
            genotype includes a missense variant.
REFERENCE   3  (bases 1 to 1336)
  AUTHORS   Yang,X., Coulombe-Huntington,J., Kang,S., Sheynkman,G.M., Hao,T.,
            Richardson,A., Sun,S., Yang,F., Shen,Y.A., Murray,R.R., Spirohn,K.,
            Begg,B.E., Duran-Frigola,M., MacWilliams,A., Pevzner,S.J.,
            Zhong,Q., Wanamaker,S.A., Tam,S., Ghamsari,L., Sahni,N., Yi,S.,
            Rodriguez,M.D., Balcha,D., Tan,G., Costanzo,M., Andrews,B.,
            Boone,C., Zhou,X.J., Salehi-Ashtiani,K., Charloteaux,B., Chen,A.A.,
            Calderwood,M.A., Aloy,P., Roth,F.P., Hill,D.E., Iakoucheva,L.M.,
            Xia,Y. and Vidal,M.
  TITLE     Widespread Expansion of Protein Interaction Capabilities by
            Alternative Splicing
  JOURNAL   Cell 164 (4), 805-817 (2016)
   PUBMED   26871637
REFERENCE   4  (bases 1 to 1336)
  AUTHORS   Moghbeli,M., Maleknejad,M., Arabi,A. and Abbaszadegan,M.R.
  TITLE     Mutational analysis of uroporphyrinogen III cosynthase gene in
            Iranian families with congenital erythropoietic porphyria
  JOURNAL   Mol Biol Rep 39 (6), 6731-6735 (2012)
   PUBMED   22350154
  REMARK    GeneRIF: A, T to C change at nucleotide 34313, leading to a
            substitution of Leucine by Proline at codon 237, was observed in
            the homozygous state in a family with congenital erythropoietic
            porphyria.
REFERENCE   5  (bases 1 to 1336)
  AUTHORS   Fortian,A., Castano,D., Gonzalez,E., Lain,A., Falcon-Perez,J.M. and
            Millet,O.
  TITLE     Structural, thermodynamic, and mechanistical studies in
            uroporphyrinogen III synthase: molecular basis of congenital
            erythropoietic porphyria
  JOURNAL   Adv Protein Chem Struct Biol 83, 43-74 (2011)
   PUBMED   21570665
  REMARK    GeneRIF: REVIEW: Structural, thermodynamic, and mechanistical
            studies in uroporphyrinogen III synthase and molecular basis of
            congenital erythropoietic porphyria
            Review article
REFERENCE   6  (bases 1 to 1336)
  AUTHORS   Erwin,A., Balwani,M. and Desnick,R.J.
  CONSRTM   Porphyrias Consortium of the NIH-Sponsored Rare Diseases Clinical
            Research Network
  TITLE     Congenital Erythropoietic Porphyria
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   24027798
REFERENCE   7  (bases 1 to 1336)
  AUTHORS   Warner,C.A., Yoo,H.W., Roberts,A.G. and Desnick,R.J.
  TITLE     Congenital erythropoietic porphyria: identification and expression
            of exonic mutations in the uroporphyrinogen III synthase gene
  JOURNAL   J Clin Invest 89 (2), 693-700 (1992)
   PUBMED   1737856
REFERENCE   8  (bases 1 to 1336)
  AUTHORS   Boulechfar,S., Da Silva,V., Deybach,J.C., Nordmann,Y.,
            Grandchamp,B. and de Verneuil,H.
  TITLE     Heterogeneity of mutations in the uroporphyrinogen III synthase
            gene in congenital erythropoietic porphyria
  JOURNAL   Hum Genet 88 (3), 320-324 (1992)
   PUBMED   1733834
REFERENCE   9  (bases 1 to 1336)
  AUTHORS   Astrin,K.H., Warner,C.A., Yoo,H.W., Goodfellow,P.J., Tsai,S.F. and
            Desnick,R.J.
  TITLE     Regional assignment of the human uroporphyrinogen III synthase
            (UROS) gene to chromosome 10q25.2----q26.3
  JOURNAL   Hum Genet 87 (1), 18-22 (1991)
   PUBMED   2037278
REFERENCE   10 (bases 1 to 1336)
  AUTHORS   Deybach,J.C., de Verneuil,H., Boulechfar,S., Grandchamp,B. and
            Nordmann,Y.
  TITLE     Point mutations in the uroporphyrinogen III synthase gene in
            congenital erythropoietic porphyria (Gunther's disease)
  JOURNAL   Blood 75 (9), 1763-1765 (1990)
   PUBMED   2331520
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DR156879.1 and BC002573.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Oct 23, 2018 this sequence version replaced NM_000375.2.
            
            Summary: The protein encoded by this gene catalyzes the fourth step
            of porphyrin biosynthesis in the heme biosynthetic pathway. Defects
            in this gene cause congenital erythropoietic porphyria (Gunther's
            disease). [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 :: SRR3476690.258208.1,
                                           SRR7346977.336370.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000368797.10/ ENSP00000357787.4
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-31                DR156879.1         11-41
            32-1336             BC002573.2         1-1305
FEATURES             Location/Qualifiers
     source          1..1336
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q26.2"
     gene            1..1336
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /note="uroporphyrinogen III synthase"
                     /db_xref="GeneID:7390"
                     /db_xref="HGNC:HGNC:12592"
                     /db_xref="MIM:606938"
     exon            1..230
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     exon            231..319
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     CDS             257..1054
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /EC_number="4.2.1.75"
                     /note="isoform 2 is encoded by transcript variant 2;
                     uroporphyrinogen-III cosynthase; hydroxymethylbilane
                     hydrolyase"
                     /codon_start=1
                     /product="uroporphyrinogen-III synthase isoform 2"
                     /protein_id="NP_000366.1"
                     /db_xref="CCDS:CCDS7648.1"
                     /db_xref="GeneID:7390"
                     /db_xref="HGNC:HGNC:12592"
                     /db_xref="MIM:606938"
                     /translation="MKVLLLKDAKEDDCGQDPYIRELGLYGLEATLIPVLSFEFLSLP
                     SFSEKLSHPEDYGGLIFTSPRAVEAAELCLEQNNKTEVWERSLKEKWNAKSVYVVGNA
                     TASLVSKIGLDTEGETCGNAEKLAEYICSRESSALPLLFPCGNLKREILPKALKDKGI
                     AMESITVYQTVAHPGIQGNLNSYYSQQGVPASITFFSPSGLTYSLKHIQELSGDNIDQ
                     IKFAAIGPTTARALAAQGLPVSCTAESPTPQALATGIRKALQPHGCC"
     exon            320..403
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     exon            404..500
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     exon            501..575
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     exon            576..650
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     exon            651..731
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     exon            732..817
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     exon            818..916
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     exon            917..1336
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1313..1318
                     /regulatory_class="polyA_signal_sequence"
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /note="hexamer: AATAAA"
     polyA_site      1336
                     /gene="UROS"
                     /gene_synonym="UROIIIS"
                     /note="major polyA site"
ORIGIN      
        1 gcatgcgcga gcgcctagct gcgcgcagcc acccacgcga ccccagtctg aggtgcgggg
       61 tcctggggcc cggcgcgggt ggccgccgcg gcccctcggg ctgcgtgggg agggggcttc
      121 cgcccctgtt gtcattgctc ctgcagcctt ttcgctggga ctgcgcgaca ccgccccccg
      181 accgggtgcc cgctgtgtgc caggccgggt gctgggcacg gtcccgcgag tgccctataa
      241 ggactgccag gcaataatga aggttctttt actgaaggat gcgaaggaag atgactgtgg
      301 ccaggatccg tatatcaggg aattaggatt atatggactt gaagccactt tgatccctgt
      361 tttatcgttt gagtttttgt ctcttcccag tttctctgag aagctttctc atcctgaaga
      421 ttacggggga ctcattttta ccagccccag agcagtggaa gcagcagagt tatgtttgga
      481 gcaaaacaat aaaactgaag tctgggaaag gtctctgaaa gaaaaatgga atgccaagtc
      541 agtgtatgtg gttggaaatg ctactgcttc tctagtgagt aaaattggcc tggatacaga
      601 aggagaaacc tgtggaaatg cagaaaagct tgcagaatat atttgttcca gggagtcctc
      661 agcactgcct cttctatttc cctgtggaaa cctcaaaaga gaaatcctgc caaaagcgct
      721 caaggacaaa gggattgcca tggaaagcat aactgtgtat cagacagttg cacacccagg
      781 aatccaaggg aacctgaaca gctactattc ccagcagggg gttccagcca gcatcacatt
      841 ttttagtccc tctggcctca catacagtct caagcacatt caggagttat ctggtgacaa
      901 tatcgatcaa attaagtttg cagccatcgg ccccactacg gctcgcgcgc tggccgccca
      961 gggccttcct gtaagctgca ctgcagagag ccccacgcca caagccctgg ccactggcat
     1021 caggaaggct ctccagcccc atggctgctg ctgagtcagc cacctagcgc tggccccatg
     1081 cagcctccct gggctgggct ggctctggat ggagccaggc atcggcaagg gctctcggga
     1141 gctgctgccg tcagactcct gcctcaagcc tgagtggaag cacctgagga ccggggatcg
     1201 ggacctgacc tggggctggc ctcaggccca cgtgcacgtg actgccctct gtggaagcca
     1261 gcttaaaccc tagccctgtg agagcttcct gtgcccagca ggaaggaagt caaataaacc
     1321 acactgacta cctgtg
//
