Home LiteratureArticle Details
PMID: 2971757 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Identification of an alternative polyadenylation site in the human C3b/C4b receptor (complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1.

The Journal of experimental medicine ·Vol. 168 ·No. 4 ·1988-10-01 ·Pages 1255-70

Hourcade D, Miesner DR, Atkinson JP, Holers VM

Abstract

The human C3b/C4b receptor or complement receptor type one (CR1) is an approximately 200-kD single chain membrane glycoprotein of human peripheral blood cells that mediates the binding, processing, and transport of C3b-bearing immune complexes and regulates the activity of the complement cascade. Analysis of partial cDNA clones has shown that the COOH terminus is composed predominantly of three tandemly repeated regions of 450 amino acids each (15). In this report, we present a cDNA sequence that encodes the NH2 terminus of CR1. It appears to have been derived from an alternatively processed transcript, caused by polyadenylation occurring at a site within an intron in the CR1 transcriptional unit. The resulting truncated messenger carries an open reading frame that would produce a short, secreted CR1 form. We present genomic sequences and Northern blots which support this hypothesis and we propose that the NH2-terminal end of CR1 is a likely location for active sites. In addition, we report evidence for a CR1-like sequence in the human genome and we present a model for the organization of CR1.

MeSH Terms
Amino Acid Sequence Base Sequence Blotting, Northern Blotting, Southern Cell Line Cloning, Molecular DNA/genetics Exons Humans Introns Molecular Sequence Data Poly A/metabolism RNA, Messenger/genetics Receptors, Complement/genetics Receptors, Complement 3b Repetitive Sequences, Nucleic Acid Sequence Homology, Nucleic Acid Transcription, Genetic
Chemicals
RNA, Messenger Receptors, Complement Receptors, Complement 3b Poly A DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hourcade D
Howard Hughes Medical Institute Laboratories, St. Louis, Missouri.
Miesner D R
Atkinson J P
Holers V M
References (51)
51 references, click to expand
  1. Circular dichroism studies of human factor H. A regulatory component of the complement system.
    Biochim Biophys Acta. 1982 Dec 6;709(1):58-64 PMID: 6217839
  2. Polymorphism of human erythrocyte C3b/C4b receptor.
    Proc Natl Acad Sci U S A. 1983 Mar;80(6):1698-702 PMID: 6572933
  3. Visualization of human C4b-binding protein and its complexes with vitamin K-dependent protein S and complement protein C4b.
    Proc Natl Acad Sci U S A. 1983 Jun;80(11):3461-5 PMID: 6222381
  4. Genetic regulation of a structural polymorphism of human C3b receptor.
    J Clin Invest. 1983 Aug;72(2):685-93 PMID: 6223944
  5. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  6. Mode of regulation of immunoglobulin mu- and delta-chain expression varies during B-lymphocyte maturation.
    Cell. 1984 Feb;36(2):329-38 PMID: 6319016
  7. Polymorphism of the human C3b/C4b receptor. Identification of a third allele and analysis of receptor phenotypes in families and patients with systemic lupus erythematosus.
    J Exp Med. 1984 Mar 1;159(3):691-703 PMID: 6230413
  8. Duplication within the haptoglobin Hp2 gene.
    Nature. 1984 May 10-16;309(5964):131-5 PMID: 6325933
  9. Complete amino acid sequence of human plasma beta 2-glycoprotein I.
    Proc Natl Acad Sci U S A. 1984 Jun;81(12):3640-4 PMID: 6587378
  10. Alternative RNA processing: determining neuronal phenotype.
    Science. 1984 Sep 21;225(4668):1315-20 PMID: 6089345
  11. Biosynthesis of the human C3b/C4b receptor during differentiation of the HL-60 cell line. Identification and characterization of a precursor molecule.
    J Clin Invest. 1984 Nov;74(5):1649-57 PMID: 6334100
  12. Polymorphism of the C3b/C4b receptor (CR1): characterization of a fourth allele.
    J Immunol. 1985 Mar;134(3):1787-9 PMID: 3155774
  13. Characterization of a soluble form of the C3b/C4b receptor (CR1) in human plasma.
    J Immunol. 1985 May;134(5):3332-8 PMID: 3156931
  14. Human genes for three complement components that regulate the activation of C3 are tightly linked.
    J Exp Med. 1985 May 1;161(5):1189-95 PMID: 3157763
  15. Membrane complement receptors specific for bound fragments of C3.
    Adv Immunol. 1985;37:217-67 PMID: 3159188
  16. Signal sequences. The limits of variation.
    J Mol Biol. 1985 Jul 5;184(1):99-105 PMID: 4032478
  17. Rapid purification of the human C3b/C4b receptor (CR1) by monoclonal antibody affinity chromatography.
    J Immunol Methods. 1985 Oct 10;82(2):303-13 PMID: 2931485
  18. Identification of a partial cDNA clone for the human receptor for complement fragments C3b/C4b.
    Proc Natl Acad Sci U S A. 1985 Nov;82(22):7711-5 PMID: 2933745
  19. Structural and functional analysis of the complement component factor H with the use of different enzymes and monoclonal antibodies to factor H.
    Biochem J. 1985 Dec 15;232(3):841-50 PMID: 2936333
  20. Structural and functional studies on C4b-binding protein, a regulatory component of the human complement system.
    Biosci Rep. 1985 Oct-Nov;5(10-11):855-65 PMID: 3938298
  21. Structural analysis of human complement protein H: homology with C4b binding protein, beta 2-glycoprotein I, and the Ba fragment of B2.
    J Immunol. 1986 May 1;136(9):3407-11 PMID: 2937845
  22. Influence of glycosylation on allelic and cell-specific Mr variation, receptor processing, and ligand binding of the human complement C3b/C4b receptor.
    J Biol Chem. 1986 May 5;261(13):5736-44 PMID: 2939068
  23. Unusual ultrastructure of complement-component-C4b-binding protein of human complement by synchrotron X-ray scattering and hydrodynamic analysis.
    Biochem J. 1986 Feb 1;233(3):799-807 PMID: 3707527
  24. Structural and functional studies on the human C3b/C4b receptor (CR1) purified by affinity chromatography using a monoclonal antibody.
    Complement. 1986;3(2):63-78 PMID: 2945695
  25. Analysis of multiple restriction fragment length polymorphisms of the gene for the human complement receptor type I. Duplication of genomic sequences occurs in association with a high molecular mass receptor allotype.
    J Exp Med. 1986 Nov 1;164(5):1531-46 PMID: 2877046
  26. 3' non-coding region sequences in eukaryotic messenger RNA.
    Nature. 1976 Sep 16;263(5574):211-4 PMID: 822353
  27. Charon phages: safer derivatives of bacteriophage lambda for DNA cloning.
    Science. 1977 Apr 8;196(4286):161-9 PMID: 847462
  28. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  29. A technique for the removal of pyroglutamic acid from the amino terminus of proteins using calf liver pyroglutamate amino peptidase.
    Biochem Biophys Res Commun. 1978 Mar 15;81(1):176-85 PMID: 26343
  30. Mapping the spliced and unspliced late lytic SV40 RNAs.
    Cell. 1978 Aug;14(4):971-82 PMID: 210961
  31. The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA.
    Cell. 1978 Dec;15(4):1157-74 PMID: 728996
  32. Human complement factor H: isolation of cDNA clones and partial cDNA sequence of the 38-kDa tryptic fragment containing the binding site for C3b.
    Eur J Immunol. 1986 Nov;16(11):1351-5 PMID: 2946589
  33. Steps in the processing of Ad2 mRNA: poly(A)+ nuclear sequences are conserved and poly(A) addition precedes splicing.
    Cell. 1978 Dec;15(4):1477-93 PMID: 729004
  34. The synthesis and processing of the messenger RNAs specifying heavy and light chain immunoglobulins in MPC-11 cells.
    Cell. 1978 Dec;15(4):1495-509 PMID: 103631
  35. The ovalbumin gene-sequence of putative control regions.
    Nucleic Acids Res. 1980 Jan 11;8(1):127-42 PMID: 6243777
  36. Nuclear RNA precursors in the processing pathway to MOPC 21 kappa light chain messenger RNA.
    J Mol Biol. 1979 Dec 25;135(4):879-91 PMID: 119874
  37. Two mRNAs can be produced from a single immunoglobulin mu gene by alternative RNA processing pathways.
    Cell. 1980 Jun;20(2):313-9 PMID: 6771020
  38. Regulation of adenovirus-2 gene expression at the level of transcriptional termination and RNA processing.
    Nature. 1981 Mar 12;290(5802):113-8 PMID: 7207591
  39. Effect of trypsinization on the activity of human factor H.
    J Immunol. 1982 Aug;129(2):647-52 PMID: 6211491
  40. The construction of cosmid libraries which can be used to transform eukaryotic cells.
    Nucleic Acids Res. 1982 Nov 11;10(21):6715-32 PMID: 6294612
  41. A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32.
    J Immunol. 1987 Jan 1;138(1):312-5 PMID: 3782802
  42. Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins.
    Nature. 1987 Feb 5-11;325(6104):545-9 PMID: 2433596
  43. Human C3b/C4b receptor (CR1). Demonstration of long homologous repeating domains that are composed of the short consensus repeats characteristics of C3/C4 binding proteins.
    J Exp Med. 1987 Apr 1;165(4):1095-112 PMID: 2951479
  44. Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement.
    Proc Natl Acad Sci U S A. 1987 Apr;84(7):2007-11 PMID: 2436222
  45. Human complement C3b/C4b receptor (CR1) mRNA polymorphism that correlates with the CR1 allelic molecular weight polymorphism.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2459-63 PMID: 3031685
  46. The superfamily of C3b/C4b-binding proteins.
    Fed Proc. 1987 May 15;46(7):2463-9 PMID: 2952524
  47. The gene encoding decay-accelerating factor (DAF) is located in the complement-regulatory locus on the long arm of chromosome 1.
    J Exp Med. 1987 Jun 1;165(6):1731-6 PMID: 2438369
  48. The polymorphism of the C3b/C4b receptor in the normal population and in patients with systemic lupus erythematosus.
    Clin Exp Immunol. 1987 Jun;68(3):570-9 PMID: 2958190
  49. The complete amino acid sequence of human complement factor H.
    Biochem J. 1988 Jan 15;249(2):593-602 PMID: 2963625
  50. A physical map of the human regulator of complement activation gene cluster linking the complement genes CR1, CR2, DAF, and C4BP.
    J Exp Med. 1988 Feb 1;167(2):664-9 PMID: 2450163
  51. Organization of the genes encoding complement receptors type 1 and 2, decay-accelerating factor, and C4-binding protein in the RCA locus on human chromosome 1.
    J Exp Med. 1988 Apr 1;167(4):1271-80 PMID: 2451706
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1988-10-01
Pages
1255-70
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2189081
Subset
IM
Grants
PHS HHS · 53095 · United States
PHS HHS · 53104 · United States
Databases
GENBANK
X14358, X14359, X14360, X14361, X14362, Y00812
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]