Immunoglobulin heavy constant alpha 1 is a immunoglobulin gene with symbol ''IGHA1''. It encodes a constant (C) segment of

Immunoglobulin A Immunoglobulin A (IgA, also referred to as sIgA in its secretory form) is an antibody that plays a role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other ty ...

heavy chain. Immunoglobulin A is an

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

that plays a critical role in immune function in the

mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...

s. 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 An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

in body secretions, IgA plays a role in defending against

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

, as well as preventing the access of foreign

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s to the immunologic system.

Discovery

IGHA1 was first described in detail in 1975, when the

primary structure Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

(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 A nucleic acid sequence is a succession of bases within the nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. This succession is denoted by a series of a set of five different letters that indicate the order of the nu ...

for the alpha-1 heavy chain constant region and the

allelic An allele is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule. Alleles can differ at a single position through single nucleotide polymorphisms (SNP), but they can also have insertions and deletions ...

alpha-2 heavy chain regions were published in 1984, and showed the genes were contained in three

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

s, 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 Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

sequence 353 residues long. The

secondary structure Protein secondary structure is the local spatial conformation of the polypeptide backbone excluding the side chains. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...

contained within this region is dominated by

beta strand The beta sheet (β-sheet, also β-pleated sheet) is a common structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone chain, backbon ...

s, which define four antiparallel

beta sheet The beta sheet (β-sheet, also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gene ...

s. These antiparallel beta-sheets are then sandwiched to form two beta-sandwiches, a typical

tertiary structure Protein tertiary structure is the three-dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains and the ...

of the immunoglobulin fold class. The two beta sheets that comprise each beta-sandwich are joined by an

alpha helix An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is al ...

on one side. These alpha helices define the

binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...

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 A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...

identified in

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

lines. The abnormality has been identified as a translocation event, where translocation between ''IGHA1'' (found on chromosome 14), and ''

FCRL4 Fc receptor-like protein 4 is a protein that in humans is encoded by the ''FCRL4'' gene. FCRL4 is an inhibitory receptor expressed on human memory B cells which resides in epithelial Epithelium or epithelial tissue is a thin, continuous, pro ...

'' (the gene sequence encoding for an inhibitory receptor, found on chromosome 1) leads to the production of a

fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this '' fusion gene'' ...

Discovery

Gene Location

Protein Structure

Pathological Information

References

Further reading