Journal Mobile Options
Table of Contents
Vol. 88, No. 1-2, 2000
Issue release date: 2000
Cytogenet Cell Genet 88:43–49 (2000)

Cloning and characterization of human FTCD on 21q22.3, a candidate gene for glutamate formiminotransferase deficiency

Solans A. · Estivill X. · de la Luna S.
Down Syndrome Research Group, Medical and Molecular Genetics Center, IRO, Hospital Duran i Reynals, Barcelona (Spain)

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in



We have identified a new human gene, FTCD, which maps to chromosome 21q22.3 and encodes the enzyme formiminotransferase cyclodeaminase, an intermediate metabolism enzyme that links histidine catabolism to folate metabolism. The major cDNA encodes a protein containing 541 amino acid residues and shows 84% identity with porcine FTCD. Several other cDNAs have been isolated, which may result from alternative splicing events and have the potential to code for three different protein isoforms. The gene is highly expressed in human fetal and adult liver. The two FTCD protein domains show high sequence similarity to two distinct open reading frames from eubacterial genomes, suggesting that eukaryotic FTCD appeared through a gene fusion event. Defects in the glutamate formiminotransferase pathway have been documented, and the deficiency is presumed to be inherited as an autosomal recessive trait. The sequence reported here may be helpful in identifying the primary defect in glutamate formiminotransferase deficiency and establishing a molecular diagnosis.   

Copyright © 2000 S. Karger AG, Basel

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucl Acids Res 25:3389–3402 (1997).
  2. Bashour AM, Bloom GS: 58K, a microtubule-binding Golgi protein, is a formiminotransferase cyclodeaminase. J biol Chem 273:19612–19617 (1998).
  3. Beaudet R, MacKenzie RE: Formiminotransferase cyclodeaminase from porcine liver: an octomeric enzyme containing bifunctional polypeptides. Biochim biophys Acta 453:151–161 (1976).

    External Resources

  4. Bloom GS, Brashear TA: A novel 58-kDa protein associates with the Golgi apparatus and microtubules. J biol Chem 264:16083–16092 (1989).
  5. Chen H, Chrast R, Rossier C, Morris MA, Lalioti MD, Antonarakis SE: Cloning of 559 potential exons of genes of human chromosome 21 by exon trapping. Genome Res 6:747–760 (1996).
  6. Cook RJ, Lloyd RS, Wagner CJ: Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase. J biol Chem 266:4965–4973 (1991).

    External Resources

  7. Dahmane N, Ghezala GA, Gosset P, Chamoun Z, Dufresne-Zacharia MC, Lopes C, Rabatel N, Gassanova-Maugenre S, Chettouh Z, Abramowski V, Fayet E, Yaspo ML, Korn B, Blouin JL, Lehrach H, Poutska A, Antonarakis SE, Sinet PM, Creau N, Delabar JM: Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome. Genomics 48:12–23 (1998).
  8. Gao YS, Alvarez C, Nelson DS, Sztul E: Molecular cloning, characterization, and dynamics of rat formiminotransferase cyclodeaminase, a Golgi-associated 58-kDa protein. J biol Chem 273:33825–33834 (1998).
  9. Guimerà J, Pucharcós C, Domènech A, Casas C, Solans A, Gallardo T, Ashley J, Lovett M, Estivill X, Pritchard M: Cosmid contig and transcriptional map of three regions of human chromosome 21q22: identification of 37 novel transcripts by direct selection. Genomics 45:59–67 (1997).
  10. Hennig D, Scales SJ, Moreau A, Murley LL, De Mey J, Kreis TE: A formiminotransferase cyclodeaminase isoform is localized to the Golgi complex and can mediate interaction of trans-Golgi network-derived vesicles with microtubules. J biol Chem 273:19602–19611 (1998).
  11. MacKenzie RE, Aldridge M, Paquin J: The bifunctional enzyme formiminotransferase-cyclodeaminase is a tetramer of dimers. J biol Chem 255:9474–9478 (1980).

    External Resources

  12. McClain LD, Carl GF, Bridgers WF: Distribution of folic acid coenzymes and folate dependent enzymes in mouse brain. J Neurochem 24:719–722 (1975).

    External Resources

  13. Murley LL, MacKenzie RE: The nucleotide sequence of porcine formiminotransferase cyclodeaminase: expression and purification from Escherichia coli. Biochemistry 34:10358–10364 (1995).

    External Resources

  14. Murley LL, Mejía NR, MacKenzie RE: The nucleotide sequence of porcine formiminotransferase cyclodeaminase: expression and purification from Escherichia coli. J biol Chem 268:22820–22824 (1993).

    External Resources

  15. Ohira M, Seki N, Nagase T, Suzuki E, Nomura N, Ohara O, Hattori M, Sakaki Y, Eki T, Murakami Y, Saito T, Ichikawa H, Ohki M: Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21. Genome Res 7:47–58 (1997).

    External Resources

  16. Paquin J, Baugh CM, MacKenzie RE: Channeling between the active sites of formiminotransferase-cyclodeaminase: binding and kinetic studies. J biol Chem 260:14925–14931 (1985).

    External Resources

  17. Rabinowitz JC, Pricer WE: Formimino-tetrahydrofolic acid and methenyltetrahydrofolic acid as intermediates in the formation of N10-formyltetrahydofolic acid. J Am chem Soc 78:5702–5710 (1956).
  18. Raziuddin A, Sarkar FH, Dutkowski R, Shulman L, Ruddle FH, Gupta SL: Receptors for human alpha and beta interferon but not for gamma interferon are specified by human chromosome 21. Proc natl Acad Sci, USA 81:5504–5508 (1984).

    External Resources

  19. Rosenblatt D: Inherited disorders of folate transport and metabolism, in Scriver CR, Beaudet AL, Sly WS, Valle D (eds): The Metabolic and Molecular Bases of Inherited Disease, pp 3111–3128 (McGraw-Hill, New York 1995).
  20. Sambrook J, Fritsch E, Maniatis T: Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor 1989).
  21. Schultz J, Milpetz F, Bork P, Ponting CP: SMART, a simple modular architecture research tool: identification of signaling domains. Proc natl Acad Sci, USA 95:5857–5864 (1998).
  22. Shane B, Stokstad E: Transport and metabolism of folates by bacteria. J biol Chem 254:2243–2253 (1975).
  23. Tabor H, Wyngarden L: The enzymatic formation of formiminotetrahydrofolic acid, 5,10-methenyltetrahydrofolic acid, and 10-formiltetrahydrofolic acid in the metabolism of formiminoglutamic acid. J biol Chem 234:1830–1846 (1959).
  24. Tassone F, Xu H, Burkin H, Wissman S, Gardiner K: cDNA selection from 10 Mb of chromosome 21 DNA: efficiency in transcriptional mapping and reflections of genome organization. Hum molec Genet 4:1509–1518 (1995).

    External Resources

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50