ANK2

ankyrin B
Ankyrin-B, also known as Ankyrin-2, is a protein which in humans is encoded by the ANK2 gene.wikipedia
75 Related Articles

Ankyrin repeat

ANKANK repeatAnkA
Ankyrin-B is a member of the ankyrin family of proteins, and is a modular protein which is composed of three structural domains: an N-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain and death domain; and a C-terminal regulatory domain which is the least conserved and subject to variation, and determines ankyrin-B activity. The membrane-binding region of ankyrin-B is composed of 24 consecutive ankyrin repeats, and it is the membrane-binding domain of ankyrins that confer functional differences among ankyrin isoforms. Further studies have shown that the beta-hairpin loops within the ankyrin repeat domain of ankyrin-B are required for the interaction with the inositol trisphosphate receptor, and a reduction of ankyrin-B in neonatal cardiomyocytes reduces the half-life of the inositol trisphosphate receptor by 3-fold and destabilizes its proper localization; all of these effects were rescued by reintroducing ankyrin-B.
ABTB1; ABTB2; ACBD6; ACTBL1; ANK1; ANK2; ANK3; ANKAR;

ANK3

ankyrin-3ankyrin Gankyrin-G
ankyrin-1 has shown to be essential in normal function of erythrocytes; however, ankyrin-B and ankyrin-3 play essential roles in the localization and membrane stabilization of ion transporters and ion channels in cardiomyocytes.
The protein encoded by this gene, ankyrin-3 is an immunologically distinct gene product from ankyrins ANK1 and ANK2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems.

Ankyrin

ankyrin repeatsANK2ankyrin repeats domain
Ankyrin-B is a member of the ankyrin family of proteins, and is a modular protein which is composed of three structural domains: an N-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain and death domain; and a C-terminal regulatory domain which is the least conserved and subject to variation, and determines ankyrin-B activity.
Ankyrins are encoded by three genes (ANK1, ANK2 and ANK3) in mammals.

Obscurin

OBSCN
Exon 43′ in ankyrin-B is specifically and predominantly expressed in cardiac muscle and harbors key residues for modulating the interaction between ankyrin-B and obscurin.
The C-terminal region of Obscurin interacts with the cytoplasmic domain of small ankyrin 1 and with the exon 43' region of ankyrin B.

Protein

proteinsproteinaceousstructural proteins
Ankyrin-B is a member of the ankyrin family of proteins, and is a modular protein which is composed of three structural domains: an N-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain and death domain; and a C-terminal regulatory domain which is the least conserved and subject to variation, and determines ankyrin-B activity. Ankyrin-B, also known as Ankyrin-2, is a protein which in humans is encoded by the ANK2 gene.

Gene

genesnumber of genesgene sequence
Ankyrin-B, also known as Ankyrin-2, is a protein which in humans is encoded by the ANK2 gene.

Cardiac muscle

myocardiumheart musclemyocardial
Exon 43′ in ankyrin-B is specifically and predominantly expressed in cardiac muscle and harbors key residues for modulating the interaction between ankyrin-B and obscurin. Ankyrin-B is ubiquitously expressed, but shows high expression in cardiac muscle. The ANK2 gene is approximately 560 kb in size and consists of 53 exons on human chromosome 4; ANK2 is also transcriptionally regulated via over 30 alternative splicing events with variable expression of isoforms in cardiac muscle. Though ubiquitously expressed, ankyrin-B shows high expression levels in cardiac muscle, and is expressed 10-fold lower levels in skeletal muscle, suggesting that ankyrin-B plays a specifically adapted functional role in cardiac muscle.

Ion channel

ion channelschannelchannels
ankyrin-1 has shown to be essential in normal function of erythrocytes; however, ankyrin-B and ankyrin-3 play essential roles in the localization and membrane stabilization of ion transporters and ion channels in cardiomyocytes. Ankyrin-B plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in cardiomyocytes, as well as in costamere structures.

Costamere

dystrophin-glycoprotein complexDPCdystrophin-associated glycoprotein complex
Ankyrin-B plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in cardiomyocytes, as well as in costamere structures.

Heart arrhythmia

cardiac arrhythmiaarrhythmiaarrhythmias
Mutations in ankyrin-B cause a dominantly-inherited, cardiac arrhythmia syndrome known as ankyrin-B syndrome as well as sick sinus syndrome; mutations have also been associated to a lesser degree with hypertrophic cardiomyopathy.

Sick sinus syndrome

sinus node dysfunctionabnormally slow sinus node
Mutations in ankyrin-B cause a dominantly-inherited, cardiac arrhythmia syndrome known as ankyrin-B syndrome as well as sick sinus syndrome; mutations have also been associated to a lesser degree with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy

hypertrophic obstructive cardiomyopathyAsymmetric septal hypertrophyFeline hypertrophic cardiomyopathy
Mutations in ankyrin-B cause a dominantly-inherited, cardiac arrhythmia syndrome known as ankyrin-B syndrome as well as sick sinus syndrome; mutations have also been associated to a lesser degree with hypertrophic cardiomyopathy.

Heart failure

congestive heart failurecardiac failurechronic heart failure
Alterations in ankyrin-B expression levels are observed in human heart failure.

Alternative splicing

alternatively splicedtranscript variantssplice variant
The ANK2 gene is approximately 560 kb in size and consists of 53 exons on human chromosome 4; ANK2 is also transcriptionally regulated via over 30 alternative splicing events with variable expression of isoforms in cardiac muscle.

N-terminus

N-terminalN terminusN-
Ankyrin-B is a member of the ankyrin family of proteins, and is a modular protein which is composed of three structural domains: an N-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain and death domain; and a C-terminal regulatory domain which is the least conserved and subject to variation, and determines ankyrin-B activity.

C-terminus

C-terminalC-terminal domainC terminus
Ankyrin-B is a member of the ankyrin family of proteins, and is a modular protein which is composed of three structural domains: an N-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain and death domain; and a C-terminal regulatory domain which is the least conserved and subject to variation, and determines ankyrin-B activity. One study showed that the death/C-terminal domain of ankyrin-B determines both the subcellular localization as well as activity in restoring normal inositol trisphosphate receptor and ryanodine receptor localization and cardiomyocyte contractility.

Protein isoform

isoformsisoformglycoform
The membrane-binding region of ankyrin-B is composed of 24 consecutive ankyrin repeats, and it is the membrane-binding domain of ankyrins that confer functional differences among ankyrin isoforms.

Skeletal muscle

skeletal musclesskeletalmuscle
Though ubiquitously expressed, ankyrin-B shows high expression levels in cardiac muscle, and is expressed 10-fold lower levels in skeletal muscle, suggesting that ankyrin-B plays a specifically adapted functional role in cardiac muscle.

ANK1

ankyrin-1small ankyrin 1
ankyrin-1 has shown to be essential in normal function of erythrocytes; however, ankyrin-B and ankyrin-3 play essential roles in the localization and membrane stabilization of ion transporters and ion channels in cardiomyocytes.

Fusion protein

chimericrecombinant fusion proteinchimeric protein
Functional insights into ankyrin-B function have come from studies employing ankyrin-B chimeric proteins.

Ryanodine receptor

ryanodine receptor (RyR)ryanodine receptor calcium release channelRyR
One study showed that the death/C-terminal domain of ankyrin-B determines both the subcellular localization as well as activity in restoring normal inositol trisphosphate receptor and ryanodine receptor localization and cardiomyocyte contractility.

Cardiac muscle cell

cardiomyocytescardiomyocytecardiac myocytes
ankyrin-1 has shown to be essential in normal function of erythrocytes; however, ankyrin-B and ankyrin-3 play essential roles in the localization and membrane stabilization of ion transporters and ion channels in cardiomyocytes. Ankyrin-B plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in cardiomyocytes, as well as in costamere structures. One study showed that the death/C-terminal domain of ankyrin-B determines both the subcellular localization as well as activity in restoring normal inositol trisphosphate receptor and ryanodine receptor localization and cardiomyocyte contractility. Further studies have shown that the beta-hairpin loops within the ankyrin repeat domain of ankyrin-B are required for the interaction with the inositol trisphosphate receptor, and a reduction of ankyrin-B in neonatal cardiomyocytes reduces the half-life of the inositol trisphosphate receptor by 3-fold and destabilizes its proper localization; all of these effects were rescued by reintroducing ankyrin-B. Moreover, a specific sequence in ankyrin-B (absent in other ankyrin isoforms) folds as an amphipathic alpha helix is required for normal levels of sodium-calcium exchanger, sodium potassium ATPase and inositol triphosphate receptor in cardiomyocytes, and is regulated by HDJ1/HSP40 binding to this region.

Contractility

contractilemyocardial contractilitycardiac contractile performance
One study showed that the death/C-terminal domain of ankyrin-B determines both the subcellular localization as well as activity in restoring normal inositol trisphosphate receptor and ryanodine receptor localization and cardiomyocyte contractility.

Half-life

half-liveshalf lifehalf lives
Further studies have shown that the beta-hairpin loops within the ankyrin repeat domain of ankyrin-B are required for the interaction with the inositol trisphosphate receptor, and a reduction of ankyrin-B in neonatal cardiomyocytes reduces the half-life of the inositol trisphosphate receptor by 3-fold and destabilizes its proper localization; all of these effects were rescued by reintroducing ankyrin-B.

Alpha helix

alpha helicesα-helicesalpha-helices
Moreover, a specific sequence in ankyrin-B (absent in other ankyrin isoforms) folds as an amphipathic alpha helix is required for normal levels of sodium-calcium exchanger, sodium potassium ATPase and inositol triphosphate receptor in cardiomyocytes, and is regulated by HDJ1/HSP40 binding to this region.