Descriptions

ACTN2 is a major F-actin cross-linking protein in both muscle and non-muscle cells and a major multivalent platform mediating interactions with many cytoskeletal or regulatory proteins. An interaction between the C-terminal region of ACTN2 and the Z-repeat motifs of Titin protein targets ACTN2 to the Z-disk. Full-length ACTN2 does not bind Z-repeats. ACTN2 has a region that acts as a pseudo-Z-repeat between the actin-binding domain (ABD) and the spectrin-like repeats (R1), and this region prevents ACTN2 from binding to the Z-repeat of Titin protein. This autoinhibition is relieved upon binding of the Z-disk lipid phosphatidylinositol-bisphosphate to the ABD of ACTN2.

Autoinhibitory domains (AIDs)

Target domain

740-892 (EF-hand domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q9Z1P2

Entry ID Method Resolution Chain Position Source
AF-Q9Z1P2-F1 Predicted AlphaFoldDB

No variants for Q9Z1P2

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9Z1P2

No associated diseases with Q9Z1P2

13 regional properties for Q9Z1P2

Type Name Position InterPro Accession
conserved_site Actinin-type actin-binding domain, conserved site 33 - 42 IPR001589-1
conserved_site Actinin-type actin-binding domain, conserved site 107 - 131 IPR001589-2
domain Calponin homology domain 31 - 135 IPR001715-1
domain Calponin homology domain 144 - 250 IPR001715-2
repeat Spectrin repeat 275 - 383 IPR002017-1
repeat Spectrin repeat 394 - 498 IPR002017-2
repeat Spectrin repeat 510 - 620 IPR002017-3
repeat Spectrin repeat 632 - 732 IPR002017-4
domain EF-hand domain 746 - 822 IPR002048
domain EF-hand, Ca insensitive 822 - 888 IPR014837
repeat Spectrin/alpha-actinin 277 - 622 IPR018159-1
repeat Spectrin/alpha-actinin 633 - 732 IPR018159-2
binding_site EF-Hand 1, calcium-binding site 759 - 771 IPR018247

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm, cytoskeleton
  • Cytoplasm, myofibril, sarcomere, Z line
  • Cell membrane
  • Cell junction
  • Cell projection, ruffle
  • Colocalizes with MYOZ2 and PPP3CA at the Z-line of heart and skeletal muscle
  • Colocalizes with PSD in membrane ruffles and central reticular structures
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

17 GO annotations of cellular component

Name Definition
brush border The dense covering of microvilli on the apical surface of an epithelial cell in tissues such as the intestine, kidney, and choroid plexus; the microvilli aid absorption by increasing the surface area of the cell.
cell junction A cellular component that forms a specialized region of connection between two or more cells, or between a cell and the extracellular matrix, or between two membrane-bound components of a cell, such as flagella.
cell projection A prolongation or process extending from a cell, e.g. a flagellum or axon.
cell-cell junction A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects.
cortical actin cytoskeleton The portion of the actin cytoskeleton, comprising filamentous actin and associated proteins, that lies just beneath the plasma membrane.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoskeleton A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
dendritic spine A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity.
fascia adherens A cell-cell junction that contains the transmembrane protein N-cadherin, which interacts with identical molecules from neighbouring cells to form a tight mechanical intercellular link; forms a large portion of the intercalated disc, the structure at which myofibrils terminate in cardiomyocytes.
focal adhesion A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ).
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
ruffle Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork.
sarcomere The repeating unit of a myofibril in a muscle cell, composed of an array of overlapping thick and thin filaments between two adjacent Z discs.
stress fiber A contractile actin filament bundle that consists of short actin filaments with alternating polarity, cross-linked by alpha-actinin and possibly other actin bundling proteins, and with myosin present in a periodic distribution along the fiber.
Z disc Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached.

11 GO annotations of molecular function

Name Definition
actin filament binding Binding to an actin filament, also known as F-actin, a helical filamentous polymer of globular G-actin subunits.
calcium ion binding Binding to a calcium ion (Ca2+).
cytoskeletal regulatory protein binding Binding to a protein involved in modulating the reorganization of the cytoskeleton.
double-stranded RNA binding Binding to double-stranded RNA.
integrin binding Binding to an integrin.
nuclear receptor coactivator activity A transcription coactivator activity that activates or increases the transcription of specific gene sets via binding to a DNA-bound nuclear receptor, either on its own or as part of a complex. Coactivators often act by altering chromatin structure and modifications. For example, one class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators. A fourth class of coactivator activity is the bridging of a DNA-binding transcription factor to the general (basal) transcription machinery. The Mediator complex, which bridges sequence-specific DNA binding transcription factors and RNA polymerase, is also a transcription coactivator.
protein domain specific binding Binding to a specific domain of a protein.
protein homodimerization activity Binding to an identical protein to form a homodimer.
structural constituent of postsynapse The action of a molecule that contributes to the structural integrity of a postsynapse.
transmembrane transporter binding Binding to a transmembrane transporter, a protein or protein complex that enables the transfer of a substance, usually a specific substance or a group of related substances, from one side of a membrane to the other.
vinculin binding Binding to vinculin, a protein found in muscle, fibroblasts, and epithelial cells that binds actin and appears to mediate attachment of actin filaments to integral proteins of the plasma membrane.

8 GO annotations of biological process

Name Definition
actin cytoskeleton organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
actin filament bundle assembly The assembly of actin filament bundles; actin filaments are on the same axis but may be oriented with the same or opposite polarities and may be packed with different levels of tightness.
actin filament network formation The assembly of a network of actin filaments; actin filaments on different axes and with differing orientations are crosslinked together to form a mesh of filaments.
actin filament organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments. Includes processes that control the spatial distribution of actin filaments, such as organizing filaments into meshworks, bundles, or other structures, as by cross-linking.
focal adhesion assembly The aggregation and bonding together of a set of components to form a focal adhesion, a complex of intracellular signaling and structural proteins that provides a structural link between the internal actin cytoskeleton and the ECM, and also function as a locus of signal transduction activity.
muscle cell development The process whose specific outcome is the progression of a muscle cell over time, from its formation to the mature structure. Muscle cell development does not include the steps involved in committing an unspecified cell to the muscle cell fate.
platelet formation The process in which platelets bud from long processes extended by megakaryocytes.
platelet morphogenesis Generation and organization of a platelet, a non-nucleated disk-shaped cell formed by extrusion from megakaryocytes, found in the blood of all mammals, and mainly involved in blood coagulation.

18 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q3ZC55 ACTN2 Alpha-actinin-2 Bos taurus (Bovine) SS
A5D7D1 ACTN4 Alpha-actinin-4 Bos taurus (Bovine) SS
Q0III9 ACTN3 Alpha-actinin-3 Bos taurus (Bovine) SS
Q3B7N2 ACTN1 Alpha-actinin-1 Bos taurus (Bovine) SS
Q90734 ACTN4 Alpha-actinin-4 Gallus gallus (Chicken) SS
P20111 ACTN2 Alpha-actinin-2 Gallus gallus (Chicken) SS
P05094 ACTN1 Alpha-actinin-1 Gallus gallus (Chicken) SS
P18091 Actn Alpha-actinin, sarcomeric Drosophila melanogaster (Fruit fly) SS
O43707 ACTN4 Alpha-actinin-4 Homo sapiens (Human) SS
Q08043 ACTN3 Alpha-actinin-3 Homo sapiens (Human) SS
P35609 ACTN2 Alpha-actinin-2 Homo sapiens (Human) EV
P12814 ACTN1 Alpha-actinin-1 Homo sapiens (Human) SS
O88990 Actn3 Alpha-actinin-3 Mus musculus (Mouse) SS
P57780 Actn4 Alpha-actinin-4 Mus musculus (Mouse) SS
Q9JI91 Actn2 Alpha-actinin-2 Mus musculus (Mouse) SS
Q7TPR4 Actn1 Alpha-actinin-1 Mus musculus (Mouse) SS
Q9QXQ0 Actn4 Alpha-actinin-4 Rattus norvegicus (Rat) SS
Q9QWN8 Sptbn2 Spectrin beta chain, non-erythrocytic 2 Rattus norvegicus (Rat) PR
10 20 30 40 50 60
MDHYDSQQTN DYMQPEEDWD RDLLLDPAWE KQQRKTFTAW CNSHLRKAGT QIENIEEDFR
70 80 90 100 110 120
DGLKLMLLLE VISGERLAKP ERGKMRVHKI SNVNKALDFI ASKGVKLVSI GAEEIVDGNV
130 140 150 160 170 180
KMTLGMIWTI ILRFAIQDIS VEETSAKEGL LLWCQRKTAP YKNVNIQNFH ISWKDGLGFC
190 200 210 220 230 240
ALIHRHRPEL IDYGKLRKDD PLTNLNTAFD VAERYLDIPK MLDAEDIVGT ARPDEKAIMT
250 260 270 280 290 300
YVSSFYHAFS GAQKAETAAN RICKVLAVNQ ENEQLMEDYE KLASDLLEWI RRTIPWLENR
310 320 330 340 350 360
VPENTMQAMQ QKLEDFRDYR RLHKPPKVQE KCQLEINFNT LQTKLRLSNR PAFMPSEGRM
370 380 390 400 410 420
VSDINNAWGC LEQAEKGYEE WLLNEIRRLE RLDHLAEKFR QKASIHEAWT DGKEAMLRQK
430 440 450 460 470 480
DYETATLSEI KALLKKHEAF ESDLAAHQDR VEQIAAIAQE LNELDYYDSP SVNARCQKIC
490 500 510 520 530 540
DQWDNLGALT QKRREALERT EKLLETIDQL YLEYAKRAAP FNNWMEGAME DLQDTFIVHT
550 560 570 580 590 600
IEEIQGLTTA HEQFKATLPD ADKERLAILG IHNEVSKIVQ TYHVNMAGTN PYTTITPQEI
610 620 630 640 650 660
NGKWDHVRQL VPRRDQALTE EHSRQQHNER LRKQFGAQAN VIGPWIQTKM EEIGRISIEM
670 680 690 700 710 720
HGTLEDQLSH LRQYEKSIVN YKPKIDQLEG DHQLIQEALI FDNKHTNYTM EHIRVGWEQL
730 740 750 760 770 780
LTTIARTINE VENQILTRDA KGISQEQMNE FRASFNHFDR DHSGTLGPEE FKACLISLGY
790 800 810 820 830 840
DIGNDPQGEA EFARIMSIVD PNRLGVVTFQ AFIDFMSRET ADTDTADQVM ASFKILAGDK
850 860 870 880 890
NYITGDELRR ELPPDQAEYC IARMAPYAGP DSVPGALDYM SFSTALYGES DL