Ankyrin 1, also known as ANK-1, and erythrocyte ankyrin, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''ANK1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Tissue distribution

The

encoded by this gene, Ankyrin 1, is the prototype of the

ankyrin Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral mem ...

family, was first discovered in

erythrocyte Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...

s, but since has also been found in brain and muscles.

Genetics

Complex patterns of alternative splicing in the regulatory domain, giving rise to different

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

of ankyrin 1 have been described, however, the precise functions of the various isoforms are not known. Alternative

polyadenylation Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In euka ...

accounting for the different sized erythrocytic ankyrin 1 mRNAs, has also been reported. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified.

Disease linkage

Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary

spherocytosis Spherocytosis is the presence of spherocytes in the blood, i.e. erythrocytes (red blood cells) that are sphere-shaped rather than bi-concave disk shaped as normal. Spherocytes are found in all hemolytic anemias to some degree. Hereditary spheroc ...

. ANK1 shows altered methylation and expression in Alzheimer's disease. A gene expression study of postmortem brains has suggested ANK1 interacts with

interferon-γ Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. ...

signalling.

Function

The ANK1 protein belongs to the

family that are believed to link the integral

membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

s to the underlying

spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma mem ...

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

and play key roles in activities such as cell motility, activation, proliferation, contact, and maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an

amino-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin-binding domain; and a carboxy-terminal regulatory domain, which is the least conserved and subject to variation. The small ANK1 (sAnk1) protein splice variants makes contacts with obscurin, a giant protein surrounding the contractile apparatus in

striated muscle Striated muscle tissue is a muscle tissue that features repeating functional units called sarcomeres. Under the microscope, sarcomeres are visible along muscle fibers, giving a striated appearance to the tissue. The two types of striated muscle a ...

Interactions

ANK1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with T-cell lymphoma invasion and metastasis-inducing protein 1,

Titin Titin (; also called connectin) is a protein that in humans is encoded by the ''TTN'' gene. The protein, which is over 1 μm in length, functions as a molecular spring that is responsible for the passive elasticity of muscle. It comprises 2 ...

RHAG Rh-associated glycoprotein (RHAG) is an ammonia transporter protein that in humans is encoded by the ''RHAG'' gene. RHAG has also recently been designated CD241 (cluster of differentiation 241). Mutations in the RHAG gene can cause stomatocytosis ...

and OBSCN.

References

External links

* * {{Cytoskeletal proteins Proteins