Biology:Immunoglobulin heavy constant alpha 1
 Generic protein structure example |
Immunoglobulin heavy constant alpha 1 is a immunoglobulin gene with symbol IGHA1.[1] It encodes a constant (C) segment of Immunoglobulin A heavy chain. Immunoglobulin A is an antibody that plays a critical role in immune function in the mucous membranes. IgA shows the same typical structure of other antibody classes, with two heavy chains and two light chains, and four distinct domains: one variable region, and three variable regions. As a major class of immunoglobulin in body secretions, IgA plays a role in defending against infection, as well as preventing the access of foreign antigens to the immunologic system.
Discovery
IGHA1 was first described in detail in 1975, when the primary structure (the amino acid sequence) of IgA was elucidated through the sequencing of tryptic and chymotryptic peptides.[2] Similarly, the primary sequence was determined independently for the alpha-2 chain of the protein in 1979.[3] Complete nucleotide sequences for the alpha-1 heavy chain constant region and the allelic alpha-2 heavy chain regions were published in 1984, and showed the genes were contained in three exons, each of which encodes a single region of the protein domain.[4]
Gene Location
The genes encoding IGHA1 are found on human chromosome 14.[5] The sequence encoding IGHA1 is 1,497 nucleotides long and is found between loci 105,707,168 and 105,708,664.[6] The annotated chromosome location is also given as 14q32.33.[7]
Protein Structure
The Ig alpha-1 chain C region is contained on the first of the constant regions of IgA, and is composed of an amino acid sequence 353 residues long.[8] The secondary structure contained within this region is dominated by beta strands, which define four antiparallel beta sheets. These antiparallel beta-sheets are then sandwiched to form two beta-sandwiches, a typical tertiary structure of the immunoglobulin fold class.[9] The two beta sheets that comprise each beta-sandwich are joined by an alpha helix on one side. These alpha helices define the binding site for this protein, with the binding site incorporating one antiparallel beta strand on either side of the helix.[8] In addition to the binding sites, the opposite side of the beta-sandwich is connected by a series of loops, which define a hypervariable loop system, that may have a role in determining the specificity of an interaction between IgA and an antigen.[10]
Pathological Information
IGHA1 has been implicated in a chromosomal abnormality identified in multiple myeloma lines.[11] The abnormality has been identified as a translocation event, where translocation between IGHA1 (found on chromosome 14), and FCRL4 (the gene sequence encoding for an inhibitory receptor, found on chromosome 1) leads to the production of a fusion protein.[12]
References
- ↑ "Entrez Gene: IGHA1 immunoglobulin heavy constant alpha 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3493.
- ↑ Kratzin, H.; Altevogt, P.; Ruban, E.; Kortt, A.; Staroscik, K.; Hilschmann, N. (1975-08-01). "[The primary structure of a monoclonal IgA-immunoglobulin (IgA Tro.), II. The amino acid sequence of the H-chain, alpha-type, subgroup III; structure of the complete IgA-molecule (author's transl)]". Hoppe-Seyler's Zeitschrift für Physiologische Chemie 356 (8): 1337–1342. ISSN 0018-4888. PMID 809331.
- ↑ Putnam, F. W.; Liu, Y. S.; Low, T. L. (1979-04-25). "Primary structure of a human IgA1 immunoglobulin. IV. Streptococcal IgA1 protease, digestion, Fab and Fc fragments, and the complete amino acid sequence of the alpha 1 heavy chain". The Journal of Biological Chemistry 254 (8): 2865–2874. doi:10.1016/S0021-9258(17)30153-9. ISSN 0021-9258. PMID 107164.
- ↑ Flanagan, J. G.; Lefranc, M. P.; Rabbitts, T. H. (1984-03-01). "Mechanisms of divergence and convergence of the human immunoglobulin alpha 1 and alpha 2 constant region gene sequences". Cell 36 (3): 681–688. doi:10.1016/0092-8674(84)90348-9. ISSN 0092-8674. PMID 6421489.
- ↑ "Genome Data Viewer". https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=3493.
- ↑ "IGHA1 immunoglobulin heavy constant alpha 1 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/3493.
- ↑ "IGHA1 Symbol Report | HUGO Gene Nomenclature Committee". https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=HGNC:5478.
- ↑ 8.0 8.1 Europe, Protein Data Bank in. "Ig alpha-1 chain C region in PDB entry 1ow0 ‹ PDBe ‹ EMBL-EBI". http://www.ebi.ac.uk/pdbe/entry/pdb/1ow0/protein/1.
- ↑ Berg, Jeremy M.; Tymoczko, John L.; Stryer, Lubert (2002-01-01) (in en). The Immunoglobulin Fold Consists of a Beta-Sandwich Framework with Hypervariable Loops. https://www.ncbi.nlm.nih.gov/books/NBK22461/.
- ↑ Sela-Culang, Inbal; Kunik, Vered; Ofran, Yanay (2013-10-08). "The Structural Basis of Antibody-Antigen Recognition". Frontiers in Immunology 4: 302. doi:10.3389/fimmu.2013.00302. ISSN 1664-3224. PMID 24115948.
- ↑ "IGHA1 - Ig alpha-1 chain C region - Homo sapiens (Human) - IGHA1 gene & protein". https://www.uniprot.org/uniprot/P01876#pathology_and_biotech.
- ↑ "Results for the protein: P01876". http://bioinf.umbc.edu/dmdm/gene_prot_page.php?search_type=protein&id=113584.
Further reading
- Kerr MA (1990). "The structure and function of human IgA.". Biochem. J. 271 (2): 285–96. doi:10.1042/bj2710285. PMID 2241915.
- "Primary structure of a human IgA1 immunoglobulin. IV. Streptococcal IgA1 protease, digestion, Fab and Fc fragments, and the complete amino acid sequence of the alpha 1 heavy chain.". J. Biol. Chem. 254 (8): 2865–74. 1979. doi:10.1016/S0021-9258(17)30153-9. PMID 107164.
- "[Rule of antibody structure. Primary structure of a human monoclonal IgA-immunoglobulin (myeloma protein Tro). VII. Purification and characterization of the disulfide bridges]". Hoppe-Seyler's Z. Physiol. Chem. 360 (12): 1919–40. 1980. PMID 393607.
- "[The primary structure of a monoclonal IgA-immunoglobulin (IgA Tro.), II. The amino acid sequence of the H-chain, alpha-type, subgroup III; structure of the complete IgA-molecule (author's transl)]". Hoppe-Seyler's Z. Physiol. Chem. 356 (8): 1337–42. 1975. PMID 809331.
- "Mechanisms of divergence and convergence of the human immunoglobulin alpha 1 and alpha 2 constant region gene sequences.". Cell 36 (3): 681–8. 1984. doi:10.1016/0092-8674(84)90348-9. PMID 6421489.
- "Structure of human immunoglobulin gamma genes: implications for evolution of a gene family.". Cell 29 (2): 671–9. 1982. doi:10.1016/0092-8674(82)90183-0. PMID 6811139.
- "Location of a novel type of interpolypeptide chain linkage in the human protein HC-IgA complex (HC-IgA) and identification of a heterogeneous chromophore associated with the complex.". J. Biol. Chem. 269 (1): 384–9. 1994. doi:10.1016/S0021-9258(17)42361-1. PMID 7506257.
- "Identification of residues in the CH2/CH3 domain interface of IgA essential for interaction with the human fcalpha receptor (FcalphaR) CD89.". J. Biol. Chem. 274 (33): 23508–14. 1999. doi:10.1074/jbc.274.33.23508. PMID 10438530.
- "Human and murine immunoglobulin expression vector cassettes.". Mol. Immunol. 37 (14): 837–45. 2001. doi:10.1016/S0161-5890(00)00101-2. PMID 11257305.
- "The role of constant region carbohydrate in the assembly and secretion of human IgD and IgA1.". J. Biol. Chem. 277 (32): 29005–11. 2002. doi:10.1074/jbc.M203258200. PMID 12023968.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "A proteomic analysis of human bile.". Mol. Cell. Proteomics 3 (7): 715–28. 2005. doi:10.1074/mcp.M400015-MCP200. PMID 15084671.
- "Effect of mutations in the human immunoglobulin A1 (IgA1) hinge on its susceptibility to cleavage by diverse bacterial IgA1 proteases.". Infect. Immun. 73 (3): 1515–22. 2005. doi:10.1128/IAI.73.3.1515-1522.2005. PMID 15731049.
- "A competitive mechanism for staphylococcal toxin SSL7 inhibiting the leukocyte IgA receptor, Fc alphaRI, is revealed by SSL7 binding at the C alpha2/C alpha3 interface of IgA.". J. Biol. Chem. 281 (3): 1389–93. 2006. doi:10.1074/jbc.M509334200. PMID 16293625.
- "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.". DNA Res. 12 (2): 117–26. 2007. doi:10.1093/dnares/12.2.117. PMID 16303743.
- "Purification, properties and extended solution structure of the complex formed between human immunoglobulin A1 and human serum albumin by scattering and ultracentrifugation.". J. Mol. Biol. 356 (2): 413–31. 2006. doi:10.1016/j.jmb.2005.11.060. PMID 16376934.
- "Large-scale mapping of human protein-protein interactions by mass spectrometry.". Mol. Syst. Biol. 3 (1): 89. 2007. doi:10.1038/msb4100134. PMID 17353931.
- "Expression of SNC73, a transcript of the immunoglobulin alpha-1 gene, in human epithelial carcinomas.". World J. Gastroenterol. 13 (16): 2305–11. 2007. doi:10.3748/wjg.v13.i16.2305. PMID 17511028.
 |  |
