Immunoglobulin heavy constant alpha 1

IGHA1
Identifiers
Aliases	IGHA1, IgA1, Immunoglobulin heavy constant alpha 1
External IDs	OMIM: 146900; GeneCards: IGHA1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1IGA, 1OW0, 2QEJ
Gene location (Human) Chr. Chromosome 14 (human) Band 14q32.33 Start 105,703,995 bp End 105,708,665 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in duodenum mucosa of transverse colon spleen rectum appendix olfactory zone of nasal mucosa tonsil bone marrow cell gallbladder lymph node n/a More reference expression data BioGPS n/a
Gene ontology Molecular function antigen binding immunoglobulin receptor binding Cellular component secretory IgA immunoglobulin complex blood microparticle monomeric IgA immunoglobulin complex secretory dimeric IgA immunoglobulin complex extracellular exosome external side of plasma membrane extracellular space extracellular region plasma membrane membrane immunoglobulin complex, circulating immunoglobulin complex Biological process B cell receptor signaling pathway receptor-mediated endocytosis phagocytosis, engulfment retina homeostasis glomerular filtration immune response complement activation, classical pathway phagocytosis, recognition positive regulation of B cell activation innate immune response positive regulation of respiratory burst leukocyte migration adaptive immune response immune system process defense response to bacterium Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 3493 n/a Ensembl ENSG00000211895 n/a UniProt P01876 n/a RefSeq (mRNA) n/a n/a RefSeq (protein) n/a n/a Location (UCSC) Chr 14: 105.7 – 105.71 Mb n/a PubMed search n/a
Wikidata
View/Edit Human

Immunoglobulin heavy constant alpha 1 is a immunoglobulin gene with symbol IGHA1. 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. 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

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.

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.

Function

The IGHA1 gene encodes the heavy-chain constant region that defines the IgA1 subclass, the antibody isotype responsible for the body's primary humoral defense at mucosal surfaces. Together with IgA2, it accounts for over half of all antibody produced in the body. This constant region promotes antigen-independent trapping of pathogens and toxins in the mucus so they can be cleared before invading the epithelium.

Clinical significance

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.

Further reading

• Kerr MA (October 1990). "The structure and function of human IgA". The Biochemical Journal. 271 (2): 285–296. doi:10.1042/bj2710285. PMC 1149552. PMID 2241915.
• Yang C, Kratzin H, Götz H, Hilschmann N (1980). "[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 Zeitschrift Fur Physiologische Chemie. 360 (12): 1919–1940. PMID 393607.
• Takahashi N, Ueda S, Obata M, Nikaido T, Nakai S, Honjo T (June 1982). "Structure of human immunoglobulin gamma genes: implications for evolution of a gene family". Cell. 29 (2): 671–679. doi:10.1016/0092-8674(82)90183-0. PMID 6811139. S2CID 31733882.
• Calero M, Escribano J, Grubb A, Méndez E (1994). "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". The Journal of Biological Chemistry. 269 (1): 384–389. doi:10.1016/S0021-9258(17)42361-1. PMID 7506257.
• Pleass RJ, Dunlop JI, Anderson CM, Woof JM (1999). "Identification of residues in the CH2/CH3 domain interface of IgA essential for interaction with the human fcalpha receptor (FcalphaR) CD89". The Journal of Biological Chemistry. 274 (33): 23508–23514. doi:10.1074/jbc.274.33.23508. PMID 10438530.
• McLean GR, Nakouzi A, Casadevall A, Green NS (2001). "Human and murine immunoglobulin expression vector cassettes". Molecular Immunology. 37 (14): 837–845. doi:10.1016/S0161-5890(00)00101-2. PMID 11257305.
• Gala FA, Morrison SL (2002). "The role of constant region carbohydrate in the assembly and secretion of human IgD and IgA1". The Journal of Biological Chemistry. 277 (32): 29005–29011. doi:10.1074/jbc.M203258200. PMID 12023968.
• Kristiansen TZ, Bunkenborg J, Gronborg M, Molina H, Thuluvath PJ, Argani P, et al. (July 2004). "A proteomic analysis of human bile". Molecular & Cellular Proteomics. 3 (7): 715–728. doi:10.1074/mcp.M400015-MCP200. PMID 15084671.
• Senior BW, Woof JM (2005). "Effect of mutations in the human immunoglobulin A1 (IgA1) hinge on its susceptibility to cleavage by diverse bacterial IgA1 proteases". Infection and Immunity. 73 (3): 1515–1522. doi:10.1128/IAI.73.3.1515-1522.2005. PMC 1064975. PMID 15731049.
• Wines BD, Willoughby N, Fraser JD, Hogarth PM (2006). "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". The Journal of Biological Chemistry. 281 (3): 1389–1393. doi:10.1074/jbc.M509334200. PMID 16293625.
• Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, et al. (2005). "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 Research. 12 (2): 117–126. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Almogren A, Furtado PB, Sun Z, Perkins SJ, Kerr MA (February 2006). "Purification, properties and extended solution structure of the complex formed between human immunoglobulin A1 and human serum albumin by scattering and ultracentrifugation". Journal of Molecular Biology. 356 (2): 413–431. doi:10.1016/j.jmb.2005.11.060. PMID 16376934.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
• Geng LY, Shi ZZ, Dong Q, Cai XH, Zhang YM, Cao W, et al. (April 2007). "Expression of SNC73, a transcript of the immunoglobulin alpha-1 gene, in human epithelial carcinomas". World Journal of Gastroenterology. 13 (16): 2305–2311. doi:10.3748/wjg.v13.i16.2305. PMC 4147138. PMID 17511028.