Alpha-actinin-2 is a
protein which in humans is encoded by the ''ACTN2''
gene.
This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and
titin to
Z-discs.
Structure
Alpha-actinin-2 is a 103.8 kDa protein composed of 894 amino acids.
Each molecule is rod-shaped (35 nm in length) and it homodimerizes in an anti-parallel fashion. Each monomer has an
N-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 ami ...
actin-binding region composed of two calponin homology domains, two
C-terminal EF hand domains, and four tandem spectrin-like repeats form the rod domain in the central region of the molecule.
The high-resolution crystal structure of human alpha-actinin 2 at 3.5 Å was recently resolved. Alpha
actinins belong to the
spectrin gene superfamily which represents a diverse group of actin-binding
cytoskeletal proteins, including
spectrin,
dystrophin,
utrophin and
fimbrin.
Skeletal, cardiac, and smooth muscle isoforms are localized to the
Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. Alpha-actinin 2 has been shown to
interact with
KCNA5,
,
[ DISC1,]MYOZ1
Myozenin-1 is a protein that in humans is encoded by the ''MYOZ1'' gene.
Interactions
MYOZ1 has been shown to interact with Telethonin, FLNC and Actinin, alpha 2
Alpha-actinin-2 is a protein which in humans is encoded by the ''ACTN2'' gene. Thi ...
,GRIN2B
Glutamate MDAreceptor subunit epsilon-2, also known as ''N''-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a protein that in humans is encoded by the ''GRIN2B'' gene.
NMDA receptors
''N''-methyl-D-aspartate (NMDA) receptors are a ...
,TTN
''ttn'' (''the total news'') was a 30 minute weekly Australian news program aimed at school-aged (9- to 14-year-old) children produced and broadcast by Network Ten from 2004 to 2008. It presented current issues and events in a way that could b ...
, NMDAR, SYNPO2
Myopodin protein, also called Synaptopodin-2 is a protein that in humans is encoded by the ''SYNPO2'' gene. Myopodin is expressed in cardiac, smooth muscle and skeletal muscle, and localizes to Z-disc structures.
Structure
Myopodin is a 117.4 ...
, LDB3, and FATZ.
Function
The primary function of alpha-actinin-2 is to crosslink filamentous actin molecules and titin molecules from adjoining sarcomeres at Z-discs, a function that is modulated by phospholipids. It is clear from studies by Hampton et al. that this crosslinking can assume a variety of conformations, with preferences for 60° and 120° angles. Alpha-actinin-2 also functions in docking signalling molecules at Z-discs, and additional studies have also implicated alpha-actinin-2 in the binding of cardiac ion channels, Kv1.5 in particular.
Clinical significance
Mutations in ''ACTN2'' are associated with hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...
, as well as dilated cardiomyopathy and endocardial fibroelastosis
Endocardial fibroelastosis (EFE) is a rare heart disorder usually occurring in children two years old and younger. It may also be considered a reaction to stress, not necessarily a specific disease.
It should not be confused with endomyocardial fi ...
. The diverse functions of alpha-actinin-2 are reflected in the diverse clinical presentation of patients carrying ''ACTN2'' mutations.
References
Further reading
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External links
Mass spectrometry characterization of human ACTN2 at COPaKB
GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview
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{{Cytoskeletal Proteins
EF-hand-containing proteins