HLA class II histocompatibility antigen, DR alpha chain is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the HLA-DRA gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1

HLA-DRB1

HLA class II histocompatibility antigen, DRB1-9 beta chain is a protein that in humans is encoded by the HLA-DRB1 gene. DRB1 encodes the most prevalent beta subunit of HLA-DR.- Function :...

, and two of any DRB3, DRB4

HLA-DRB4

Major histocompatibility complex, class II, DR beta 4, also known as HLA-DRB4, is a human gene.- Function :The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha and a beta chain , both anchored in the...

, or DRB5

HLA-DRB5

HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 gene.- Function :The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha and a beta chain , both...

 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms (2 alleles of DRB1 and two alleles from DRB3, DRB4 or DRB5).

Function

The polypeptide subunit

Protein subunit

In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...

 encoded by this gene belongs to the HLA class II

MHC class II

MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells ....

 alpha chain paralogues. The class II protein is a heterodimer consisting of an alpha (DRα) and a beta chain (DRβ), both anchored in the membrane. It plays a central role in the immune system

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cell

Antigen-presenting cell

An antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...

s (APC: B lymphocytes, dendritic cells, macrophages).

Gene structure and polymorphisms

The alpha chain is approximately 33-35 kDa and its gene contains 5 exon

Exon

An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...

s. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains

Protein domain

A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...

, and exon 4 encodes the transmembrane

Transmembrane protein

A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...

 domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1

HLA-DRB1

HLA class II histocompatibility antigen, DRB1-9 beta chain is a protein that in humans is encoded by the HLA-DRB1 gene. DRB1 encodes the most prevalent beta subunit of HLA-DR.- Function :...

, DRB3, DRB4

HLA-DRB4

Major histocompatibility complex, class II, DR beta 4, also known as HLA-DRB4, is a human gene.- Function :The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha and a beta chain , both anchored in the...

 and DRB5

HLA-DRB5

HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 gene.- Function :The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha and a beta chain , both...

.

Alleles

There are two different HLA-DRA chains in the human population coded by three different DRA alleles:

DRA*01:01 DRA*01:02:01 DRA*01:02:02

Further reading