Immunoglobulin heavy constant alpha 1

Immunoglobulin heavy constant alpha 1 is a immunoglobulin gene with symbol IGHA1.[3] 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.

IGHA1
Identifiers
AliasesIGHA1, IgA1, Immunoglobulin heavy constant alpha 1
External IDsOMIM: 146900 GeneCards: IGHA1
Orthologs
SpeciesHumanMouse
Entrez

3493

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Ensembl

ENSG00000211895

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)Chr 14: 105.7 – 105.71 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

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.[4] Similarly, the primary sequence was determined independently for the alpha-2 chain of the protein in 1979.[5] 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.[6]

Gene Location

The genes encoding IGHA1 are found on human chromosome 14.[7] The sequence encoding IGHA1 is 1,497 nucleotides long and is found between loci 105,707,168 and 105,708,664.[8] The annotated chromosome location is also given as 14q32.33.[9]

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.[10] 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.[11] 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.[10] 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.[12]

Pathological Information

IGHA1 has been implicated in a chromosomal abnormality identified in multiple myeloma lines.[13] 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.[14]

References
  1. GRCh38: Ensembl release 89: ENSG00000211895 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Entrez Gene: IGHA1 immunoglobulin heavy constant alpha 1".
  4. 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.
  5. 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.
  6. 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. S2CID 54312675.
  7. "Genome Data Viewer". www.ncbi.nlm.nih.gov. Retrieved 2016-10-16.
  8. "IGHA1 immunoglobulin heavy constant alpha 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-16.
  9. "IGHA1 Symbol Report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2016-10-16.
  10. Europe, Protein Data Bank in. "Ig alpha-1 chain C region in PDB entry 1ow0 ‹ PDBe ‹ EMBL-EBI". www.ebi.ac.uk. Retrieved 2016-10-16.
  11. Berg, Jeremy M.; Tymoczko, John L.; Stryer, Lubert (2002-01-01). "The Immunoglobulin Fold Consists of a Beta-Sandwich Framework with Hypervariable Loops". {{cite journal}}: Cite journal requires |journal= (help)
  12. 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. PMC 3792396. PMID 24115948.
  13. "IGHA1 - Ig alpha-1 chain C region - Homo sapiens (Human) - IGHA1 gene & protein". www.uniprot.org. Retrieved 2016-10-16.
  14. "Results for the protein: P01876". bioinf.umbc.edu. Retrieved 2016-10-16.

Further reading
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