P57780
SS
Gene name |
Actn4 |
Protein name |
Alpha-actinin-4 |
Names |
Non-muscle alpha-actinin 4 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:60595 |
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 |
760-912 (EF-hand domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for P57780
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P57780-F1 | Predicted | AlphaFoldDB |
39 variants for P57780
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs211928908 | 16 | N>S | No | EVA | |
| rs3388882546 | 61 | C>F | No | EVA | |
| rs3388854182 | 71 | Q>* | No | EVA | |
| rs3388890505 | 92 | I>T | No | EVA | |
| rs3388898000 | 108 | H>Y | No | EVA | |
| rs3388892959 | 134 | E>K | No | EVA | |
| rs3388882614 | 160 | S>T | No | EVA | |
| rs3397707294 | 164 | T>A | No | EVA | |
| rs3396932404 | 164 | T>I | No | EVA | |
| rs3388869739 | 255 | E>K | No | EVA | |
| rs3507866483 | 271 | G>V | No | EVA | |
| rs3388900305 | 310 | I>N | No | EVA | |
| rs3388900306 | 330 | Q>L | No | EVA | |
| rs3388900322 | 380 | M>K | No | EVA | |
| rs3397696793 | 409 | L>P | No | EVA | |
| rs3388896794 | 421 | Q>* | No | EVA | |
| rs3388896783 | 434 | E>D | No | EVA | |
| rs3388854179 | 451 | K>N | No | EVA | |
| rs3397699629 | 497 | Q>L | No | EVA | |
| rs3388892948 | 523 | Q>H | No | EVA | |
| rs3388898016 | 526 | T>S | No | EVA | |
| rs3388900330 | 560 | T>I | No | EVA | |
| rs3397458099 | 579 | P>S | No | EVA | |
| rs3397725606 | 582 | D>G | No | EVA | |
| rs3397677195 | 584 | E>V | No | EVA | |
| rs3388854028 | 616 | T>A | No | EVA | |
| rs3388890441 | 618 | Q>H | No | EVA | |
| rs3388895214 | 627 | V>L | No | EVA | |
| rs3388900292 | 644 | K>N | No | EVA | |
| rs3388900356 | 663 | G>W | No | EVA | |
| rs3388895191 | 698 | I>V | No | EVA | |
| rs3388895183 | 699 | V>M | No | EVA | |
| rs3388897957 | 708 | L>M | No | EVA | |
| rs3388895235 | 715 | I>N | No | EVA | |
| rs3388890436 | 740 | L>M | No | EVA | |
| rs3388882544 | 765 | Q>P | No | EVA | |
| rs3388896763 | 785 | A>E | No | EVA | |
| rs3388898903 | 805 | D>V | No | EVA | |
| rs3388898893 | 807 | Q>* | No | EVA |
No associated diseases with P57780
5 regional properties for P57780
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | PAS domain | 121 - 232 | IPR000014-1 |
| domain | PAS domain | 335 - 402 | IPR000014-2 |
| domain | Protein kinase domain | 999 - 1251 | IPR000719 |
| active_site | Serine/threonine-protein kinase, active site | 1124 - 1136 | IPR008271 |
| binding_site | Protein kinase, ATP binding site | 1005 - 1032 | IPR017441 |
Functions
16 GO annotations of cellular component
| Name | Definition |
|---|---|
| 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. |
| cortical cytoskeleton | The portion of the cytoskeleton that lies just beneath the plasma membrane. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| 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). |
| neuron projection | A prolongation or process extending from a nerve cell, e.g. an axon or dendrite. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| perinuclear region of cytoplasm | Cytoplasm situated near, or occurring around, the nucleus. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
| pseudopodium | A temporary protrusion or retractile process of a cell, associated with flowing movements of the protoplasm, and serving for locomotion and feeding. |
| ribonucleoprotein complex | A macromolecular complex that contains both RNA and protein molecules. |
| 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. |
6 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+). |
| 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-containing complex binding | Binding to a macromolecular complex. |
| structural constituent of cytoskeleton | The action of a molecule that contributes to the structural integrity of a cytoskeletal structure. |
| ubiquitin protein ligase binding | Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins. |
13 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. |
| bicellular tight junction assembly | The aggregation, arrangement and bonding together of a set of components to form a 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. |
| gene expression | The process in which a gene's sequence is converted into a mature gene product (protein or RNA). This includes the production of an RNA transcript and its processing, translation and maturation for protein-coding genes. |
| glomerulus development | The progression of the glomerulus over time from its initial formation until its mature state. The glomerulus is a capillary tuft which forms a close network with the visceral epithelium (podocytes) and the mesangium to form the filtration barrier and is surrounded by Bowman's capsule in nephrons of the vertebrate kidney. The glomerulus is part of the nephron and is restricted to one body segment. |
| 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. |
| peroxisome proliferator activated receptor signaling pathway | The series of molecular signals initiated by binding of a ligand to any of the peroxisome proliferator activated receptors (alpha, beta or gamma) in the nuclear membrane, and ending with the initiation or termination of the transcription of target genes. |
| podocyte cell migration | The orderly movement of a podocyte from one site to another, often during the development of a multicellular organism or multicellular structure. A podocyte is a specialized kidney epithelial cell. |
| positive regulation of pinocytosis | Any process that activates, maintains or increases the rate of pinocytosis. Pinocytosis is the process in which cells take in liquid material from their external environment; literally 'cell drinking'. Liquid is enclosed in vesicles, formed by invagination of the plasma membrane. These vesicles then move into the cell and pass their contents to endosomes. |
| protein localization to bicellular tight junction | A process in which a protein is transported to, or maintained in, a location within a bicellular tight junction. |
| protein transport | The directed movement of proteins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| regulation of apoptotic process | Any process that modulates the occurrence or rate of cell death by apoptotic process. |
| retinoic acid receptor signaling pathway | The series of molecular signals generated as a consequence of a retinoic acid receptor binding to one of its physiological ligands. |
19 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 |
| P05094 | ACTN1 | Alpha-actinin-1 | Gallus gallus (Chicken) | 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 |
| P12814 | ACTN1 | Alpha-actinin-1 | Homo sapiens (Human) | SS |
| P35609 | ACTN2 | Alpha-actinin-2 | Homo sapiens (Human) | EV |
| O43707 | ACTN4 | Alpha-actinin-4 | Homo sapiens (Human) | SS |
| O88990 | Actn3 | Alpha-actinin-3 | Mus musculus (Mouse) | SS |
| Q7TPR4 | Actn1 | Alpha-actinin-1 | Mus musculus (Mouse) | SS |
| Q9JI91 | Actn2 | Alpha-actinin-2 | Mus musculus (Mouse) | SS |
| Q62261 | Sptbn1 | Spectrin beta chain, non-erythrocytic 1 | Mus musculus (Mouse) | PR |
| P15508 | Sptb | Spectrin beta chain, erythrocytic | Mus musculus (Mouse) | PR |
| Q9Z1P2 | Actn1 | Alpha-actinin-1 | Rattus norvegicus (Rat) | SS |
| Q9QXQ0 | Actn4 | Alpha-actinin-4 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MVDYHAANQA | YQYGPNSGGG | NGAGGGGSMG | DYMAQEDDWD | RDLLLDPAWE | KQQRKTFTAW |
| 70 | 80 | 90 | 100 | 110 | 120 |
| CNSHLRKAGT | QIENIDEDFR | DGLKLMLLLE | VISGERLPKP | ERGKMRVHKI | NNVNKALDFI |
| 130 | 140 | 150 | 160 | 170 | 180 |
| ASKGVKLVSI | GAEEIVDGNA | KMTLGMIWTI | ILRFAIQDIS | VEETSAKEGL | LLWCQRKTAP |
| 190 | 200 | 210 | 220 | 230 | 240 |
| YKNVNVQNFH | ISWKDGLAFN | ALIHRHRPEL | IEYDKLRKDD | PVTNLNNAFE | VAEKYLDIPK |
| 250 | 260 | 270 | 280 | 290 | 300 |
| MLDAEDIVNT | ARPDEKAIMT | YVSSFYHAFS | GAQKAETAAN | RICKVLAVNQ | ENEHLMEDYE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| RLASDLLEWI | RRTIPWLEDR | VPQKTIQEMQ | QKLEDFRDYR | RVHKPPKVQE | KCQLEINFNT |
| 370 | 380 | 390 | 400 | 410 | 420 |
| LQTKLRLSNR | PAFMPSEGRM | VSDINNGWQH | LEQAEKGYEE | WLLNEIRRLE | RLDHLAEKFR |
| 430 | 440 | 450 | 460 | 470 | 480 |
| QKASIHEAWT | DGKEAMLKQR | DYETATLSDI | KALIRKHEAF | ESDLAAHQDR | VEQIAAIAQE |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LNELDYYDSH | NVNTRCQKIC | DQWDNLGSLT | HSRREALEKT | EKQLETIDQL | HLEYAKRAAP |
| 550 | 560 | 570 | 580 | 590 | 600 |
| FNNWMESAME | DLQDMFIVHT | IEEIEGLISA | HDQFKSTLPD | ADREREAILA | IHKEAQRIAE |
| 610 | 620 | 630 | 640 | 650 | 660 |
| SNHIKLSGSN | PYTTVTPQII | NSKWEKVQQL | VPKRDHALLE | EQSKQQSNEH | LRRQFASQAN |
| 670 | 680 | 690 | 700 | 710 | 720 |
| MVGPWIQTKM | EEIGRISIEM | NGTLEDQLSH | LKQYERSIVD | YKPSLDLLEQ | QHQLIQEALI |
| 730 | 740 | 750 | 760 | 770 | 780 |
| FDNKHTNYTM | EHIRVGWEQL | LTTIARTINE | VENQILTRDA | KGISQEQMQE | FRASFNHFDK |
| 790 | 800 | 810 | 820 | 830 | 840 |
| DHGGALGPEE | FKACLISLGY | DVENDRQGDA | EFNRIMSVVD | PNHSGLVTFQ | AFIDFMSRET |
| 850 | 860 | 870 | 880 | 890 | 900 |
| TDTDTADQVI | ASFKVLAGDK | NFITAEELRR | ELPPDQAEYC | IARMAPYQGP | DAAPGALDYK |
| 910 | |||||
| SFSTALYGES | DL |