Immunoglobulin heavy constant alpha 1

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. Similarly, the primary sequence was determined independently for the alpha-2 chain of the protein in 1979. 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.

Gene Location

The genes encoding IGHA1 are found on human chromosome 14. The sequence encoding IGHA1 is 1,497 nucleotides long and is found between loci 105,707,168 and 105,708,664. The annotated chromosome location is also given as 14q32.33.

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. 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. 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. 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.

Pathological Information

IGHA1 has been implicated in a chromosomal abnormality identified in multiple myeloma lines. 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.

References

References

1. "Entrez Gene: IGHA1 immunoglobulin heavy constant alpha 1".
2. (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.
3. (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.
4. (1984-03-01). "Mechanisms of divergence and convergence of the human immunoglobulin alpha 1 and alpha 2 constant region gene sequences". Cell.
5. "Genome Data Viewer".
6. "IGHA1 immunoglobulin heavy constant alpha 1 [Homo sapiens (human)] - Gene - NCBI".
7. "IGHA1 Symbol Report {{!}} HUGO Gene Nomenclature Committee".
8. Europe, Protein Data Bank in. "Ig alpha-1 chain C region in PDB entry 1ow0 ‹ PDBe ‹ EMBL-EBI".
9. (2002-01-01). "The Immunoglobulin Fold Consists of a Beta-Sandwich Framework with Hypervariable Loops".
10. (2013-10-08). "The Structural Basis of Antibody-Antigen Recognition". Frontiers in Immunology.
11. "IGHA1 - Ig alpha-1 chain C region - Homo sapiens (Human) - IGHA1 gene & protein".
12. "Results for the protein: P01876".