P05094
SS
Gene name |
ACTN1 |
Protein name |
Alpha-actinin-1 |
Names |
Alpha-actinin cytoskeletal isoform , F-actin cross-linking protein , Non-muscle alpha-actinin-1 |
Species |
Gallus gallus (Chicken) |
KEGG Pathway |
gga:373918 |
EC number |
|
Protein Class |
|
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 |
741-893 (EF-hand domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
2 structures for P05094
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 1SJJ | EM | 2000 A | A/B | 26-893 | PDB |
| AF-P05094-F1 | Predicted | AlphaFoldDB |
28 variants for P05094
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs1059203148 | 18 | E>D | No | EVA | |
| rs315788928 | 42 | C>G | No | EVA | |
| rs16483373 | 232 | A>G | No | EVA | |
| rs733816457 | 290 | W>G | No | EVA | |
| rs732019004 | 294 | T>P | No | EVA | |
| rs16483383 | 300 | N>D | No | EVA | |
| rs16483386 | 302 | A>G | No | EVA | |
| rs16483385 | 302 | A>T | No | EVA | |
| rs16483389 | 304 | E>Q | No | EVA | |
| rs16483390 | 305 | N>K | No | EVA | |
| rs16483391 | 307 | M>I | No | EVA | |
| rs16483393 | 309 | A>D | No | EVA | |
| rs738113112 | 316 | D>A | No | EVA | |
| rs740117267 | 317 | F>S | No | EVA | |
| rs731253208 | 319 | D>A | No | EVA | |
| rs16483399 | 323 | L>V | No | EVA | |
| rs734490887 | 445 | L>R | No | EVA | |
| rs735596860 | 549 | T>P | No | EVA | |
| rs737663736 | 569 | I>L | No | EVA | |
| rs794236877 | 596 | I>V | No | EVA | |
| rs732833075 | 597 | T>P | No | EVA | |
| rs735194684 | 639 | Q>K | No | EVA | |
| rs1059342626 | 695 | Q>L | No | EVA | |
| rs1059188536 | 696 | I>M | No | EVA | |
| rs1059820703 | 696 | I>V | No | EVA | |
| rs736970546 | 710 | T>P | No | EVA | |
| rs316519697 | 732 | V>G | No | EVA | |
| rs739453187 | 852 | E>G | No | EVA |
No associated diseases with P05094
13 regional properties for P05094
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| conserved_site | Actinin-type actin-binding domain, conserved site | 34 - 43 | IPR001589-1 |
| conserved_site | Actinin-type actin-binding domain, conserved site | 108 - 132 | IPR001589-2 |
| domain | Calponin homology domain | 32 - 136 | IPR001715-1 |
| domain | Calponin homology domain | 145 - 251 | IPR001715-2 |
| repeat | Spectrin repeat | 276 - 384 | IPR002017-1 |
| repeat | Spectrin repeat | 395 - 499 | IPR002017-2 |
| repeat | Spectrin repeat | 511 - 620 | IPR002017-3 |
| repeat | Spectrin repeat | 633 - 733 | IPR002017-4 |
| domain | EF-hand domain | 747 - 823 | IPR002048 |
| domain | EF-hand, Ca insensitive | 823 - 889 | IPR014837 |
| repeat | Spectrin/alpha-actinin | 278 - 623 | IPR018159-1 |
| repeat | Spectrin/alpha-actinin | 634 - 733 | IPR018159-2 |
| binding_site | EF-Hand 1, calcium-binding site | 760 - 772 | IPR018247 |
19 GO annotations of cellular component
| Name | Definition |
|---|---|
| bicellular tight junction | An occluding cell-cell junction that is composed of a branching network of sealing strands that completely encircles the apical end of each cell in an epithelial sheet; the outer leaflets of the two interacting plasma membranes are seen to be tightly apposed where sealing strands are present. Each sealing strand is composed of a long row of transmembrane adhesion proteins embedded in each of the two interacting plasma membranes. |
| 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 leading edge | The area of a motile cell closest to the direction of movement. |
| cell projection | A prolongation or process extending from a cell, e.g. a flagellum or axon. |
| cortical actin cytoskeleton | The portion of the actin cytoskeleton, comprising filamentous actin and associated proteins, that lies just beneath the plasma membrane. |
| dense body | An electron dense body which may contain granules. |
| 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). |
| inner dense plaque of desmosome | The desmosomal part containing the C-termini of desmoplakins which interact with the keratin intermediate filaments, serving to tether the intermediate filaments to the plasma membrane. |
| lamellipodium | A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments. |
| lateral plasma membrane | The portion of the plasma membrane at the lateral side of the cell. In epithelial cells, lateral plasma membranes are on the sides of cells which lie at the interface of adjacent cells. |
| outer dense plaque of desmosome | The desmosomal part containing plakoglobins, plakophilins, the N-termini of desmoplakins, as well as the cytoplasmic tails of the desmosomal cadherins, which together attach the plaque to the plasma membrane. |
| 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. |
| sarcolemma | The outer membrane of a muscle cell, consisting of the plasma membrane, a covering basement membrane (about 100 nm thick and sometimes common to more than one fiber), and the associated loose network of collagen fibers. |
| smooth muscle dense body | Electron-dense region associated with a smooth muscle contractile fiber. |
| 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. |
| terminal web | An actin-rich cytoskeletal network located beneath the microvilli of the apical plasma membrane of polarized epithelial cells. In addition to actin filaments, the terminal web may contain actin-binding proteins, myosin motor proteins, and intermediate filaments. The terminal web can function as a contractile structure that influences the spatial distribution of microvilli as well as the development and morphogenesis of tissues containing polarized epithelial cells. |
| Z disc | Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached. |
| zonula adherens | A cell-cell adherens junction which forms a continuous belt near the apex of epithelial cells. |
7 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. |
| alpha-actinin binding | Binding to alpha-actinin, one of a family of proteins that cross-link F-actin as antiparallel homodimers. Alpha-actinin has a molecular mass of 93-103 KDa; at the N-terminus there are two calponin homology domains, at the C-terminus there are two EF-hands. These two domains are connected by the rod domain. This domain is formed by triple-helical spectrin repeats. |
| calcium ion binding | Binding to a calcium ion (Ca2+). |
| LIM domain binding | Binding to a LIM domain (for Lin-11 Isl-1 Mec-3) of a protein, a domain with seven conserved cysteine residues and a histidine, that binds two zinc ions and acts as an interface for protein-protein interactions. |
| phosphoprotein binding | Binding to a phosphorylated protein. |
| protein homodimerization activity | Binding to an identical protein to form a homodimer. |
| 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. |
4 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. |
| 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. |
| sarcomere organization | The myofibril assembly process that results in the organization of muscle actomyosin into sarcomeres. The sarcomere is 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. |
| skeletal muscle fiber development | The process whose specific outcome is the progression of the skeletal muscle fiber over time, from its formation to the mature structure. Muscle fibers are formed by the maturation of myotubes. They can be classed as slow, intermediate/fast or fast. |
17 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| 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 |
| Q3ZC55 | ACTN2 | Alpha-actinin-2 | Bos taurus (Bovine) | SS |
| P20111 | ACTN2 | Alpha-actinin-2 | Gallus gallus (Chicken) | SS |
| Q90734 | ACTN4 | Alpha-actinin-4 | Gallus gallus (Chicken) | SS |
| P18091 | Actn | Alpha-actinin, sarcomeric | Drosophila melanogaster (Fruit fly) | SS |
| Q08043 | ACTN3 | Alpha-actinin-3 | Homo sapiens (Human) | SS |
| O43707 | ACTN4 | Alpha-actinin-4 | 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 |
| Q9Z1P2 | Actn1 | Alpha-actinin-1 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MDHHYDPQQT | NDYMQPEEDW | DRDLLLDPAW | EKQQRKTFTA | WCNSHLRKAG | TQIENIEEDF |
| 70 | 80 | 90 | 100 | 110 | 120 |
| RDGLKLMLLL | EVISGERLAK | PERGKMRVHK | ISNVNKALDF | IASKGVKLVS | IGAEEIVDGN |
| 130 | 140 | 150 | 160 | 170 | 180 |
| VKMTLGMIWT | IILRFAIQDI | SVEETSAKEG | LLLWCQRKTA | PYKNVNIQNF | HISWKDGLGF |
| 190 | 200 | 210 | 220 | 230 | 240 |
| CALIHRHRPE | LIDYGKLRKD | DPLTNLNTAF | DVAEKYLDIP | KMLDAEDIVG | TARPDEKAIM |
| 250 | 260 | 270 | 280 | 290 | 300 |
| TYVSSFYHAF | SGAQKAETAA | NRICKVLAVN | QENEQLMEDY | EKLASDLLEW | IRRTIPWLEN |
| 310 | 320 | 330 | 340 | 350 | 360 |
| RAPENTMQAM | QQKLEDFRDY | RRLHKPPKVQ | EKCQLEINFN | TLQTKLRLSN | RPAFMPSEGK |
| 370 | 380 | 390 | 400 | 410 | 420 |
| MVSDINNAWG | GLEQAEKGYE | EWLLNEIRRL | ERLDHLAEKF | RQKASIHESW | TDGKEAMLQQ |
| 430 | 440 | 450 | 460 | 470 | 480 |
| KDYETATLSE | IKALLKKHEA | FESDLAAHQD | RVEQIAAIAQ | ELNELDYYDS | PSVNARCQKI |
| 490 | 500 | 510 | 520 | 530 | 540 |
| CDQWDNLGAL | TQKRREALER | TEKLLETIDQ | LYLEYAKRAA | PFNNWMEGAM | EDLQDTFIVH |
| 550 | 560 | 570 | 580 | 590 | 600 |
| TIEEIQGLTT | AHEQFKATLP | DADKERQAIL | GIHNEVSKIV | QTYHVNMAGT | NPYTTITPQE |
| 610 | 620 | 630 | 640 | 650 | 660 |
| INGKWEHVRQ | LVPRRDQALM | EEHARQQQNE | RLRKQFGAQA | NVIGPWIQTK | MEEIGRISIE |
| 670 | 680 | 690 | 700 | 710 | 720 |
| MHGTLEDQLN | HLRQYEKSIV | NYKPKIDQLE | GDHQQIQEAL | IFDNKHTNYT | MEHIRVGWEQ |
| 730 | 740 | 750 | 760 | 770 | 780 |
| LLTTIARTIN | EVENQILTRD | AKGISQEQMN | EFRASFNHFD | RDHSGTLGPE | EFKACLISLG |
| 790 | 800 | 810 | 820 | 830 | 840 |
| YDIGNDAQGE | AEFARIMSIV | DPNRMGVVTF | QAFIDFMSRE | TADTDTADQV | MASFKILAGD |
| 850 | 860 | 870 | 880 | 890 | |
| KNYITVDELR | RELPPDQAEY | CIARMAPYNG | RDAVPGALDY | MSFSTALYGE | SDL |