O88990
SS
Gene name |
Actn3 |
Protein name |
Alpha-actinin-3 |
Names |
Alpha-actinin skeletal muscle isoform 3 , F-actin cross-linking protein |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:11474 |
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 |
753-900 (EF-hand domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for O88990
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-O88990-F1 | Predicted | AlphaFoldDB |
49 variants for O88990
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389465447 | 6 | Q>* | No | EVA | |
| rs1133383669 | 12 | A>T | No | EVA | |
| rs3389532094 | 20 | G>D | No | EVA | |
| rs3389474674 | 46 | Q>R | No | EVA | |
| rs3406965400 | 55 | N>D | No | EVA | |
| rs3408893796 | 58 | L>V | No | EVA | |
| rs3407895000 | 59 | R>S | No | EVA | |
| rs3408893800 | 62 | G>V | No | EVA | |
| rs3389425426 | 67 | N>K | No | EVA | |
| rs3389465411 | 102 | K>T | No | EVA | |
| rs3389483990 | 103 | I>F | No | EVA | |
| rs3389532078 | 122 | S>P | No | EVA | |
| rs3389518487 | 161 | E>K | No | EVA | |
| rs3389474722 | 175 | R>H | No | EVA | |
| rs3389527512 | 269 | E>K | No | EVA | |
| rs3389509168 | 283 | Q>H | No | EVA | |
| rs3408725828 | 297 | S>R | No | EVA | |
| rs3389509141 | 323 | Q>L | No | EVA | |
| rs224581886 | 324 | R>H | No | EVA | |
| rs3389516898 | 324 | R>S | No | EVA | |
| rs3389516879 | 350 | N>H | No | EVA | |
| rs3389473512 | 366 | F>I | No | EVA | |
| rs3389532117 | 381 | W>* | No | EVA | |
| rs3389516870 | 407 | H>Y | No | EVA | |
| rs3408845452 | 414 | Q>A | No | EVA | |
| rs3389425416 | 419 | H>Y | No | EVA | |
| rs3389511116 | 422 | W>L | No | EVA | |
| rs3389532136 | 450 | H>N | No | EVA | |
| rs3408995755 | 486 | N>H | No | EVA | |
| rs232492592 | 487 | S>N | No | EVA | |
| rs3408961511 | 490 | Q>L | No | EVA | |
| rs3409086068 | 534 | F>L | No | EVA | |
| rs3389484061 | 537 | W>G | No | EVA | |
| rs3408845457 | 561 | L>P | No | EVA | |
| rs3389532162 | 575 | D>A | No | EVA | |
| rs3389509167 | 589 | Q>H | No | EVA | |
| rs37363125 | 591 | I>M | No | EVA | |
| rs3389509101 | 596 | G>R | No | EVA | |
| rs37587382 | 620 | V>D | No | EVA | |
| rs3389511049 | 631 | L>P | No | EVA | |
| rs3389497119 | 632 | Q>L | No | EVA | |
| rs3389518529 | 698 | I>F | No | EVA | |
| rs3389473493 | 762 | N>Y | No | EVA | |
| rs3389511778 | 835 | E>D | No | EVA | |
| rs3389509107 | 839 | A>T | No | EVA | |
| rs3413143486 | 864 | Q>* | No | EVA | |
| rs3389511773 | 880 | A>D | No | EVA | |
| rs3412878857 | 889 | A>V | No | EVA | |
| rs3389484066 | 898 | S>N | No | EVA |
No associated diseases with O88990
9 regional properties for O88990
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Zinc finger, TAZ-type | 347 - 433 | IPR000197-1 |
| domain | Zinc finger, TAZ-type | 1765 - 1846 | IPR000197-2 |
| domain | Zinc finger, ZZ-type | 1701 - 1750 | IPR000433 |
| domain | Bromodomain | 1084 - 1194 | IPR001487 |
| domain | Coactivator CBP, KIX domain | 587 - 667 | IPR003101 |
| domain | CREB-binding protein/p300, atypical RING domain | 1192 - 1278 | IPR010303 |
| domain | Nuclear receptor coactivator, CREB-bp-like, interlocking | 2014 - 2113 | IPR014744 |
| conserved_site | Bromodomain, conserved site | 1108 - 1167 | IPR018359 |
| domain | CBP/p300-type histone acetyltransferase domain | 1323 - 1700 | IPR031162 |
9 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. |
| cortical actin cytoskeleton | The portion of the actin cytoskeleton, comprising filamentous actin and associated proteins, that lies just beneath the plasma membrane. |
| 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). |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| 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. |
| striated muscle thin filament | Filaments formed of actin and associated proteins; attached to Z discs at either end of sarcomeres in myofibrils. |
| Z disc | Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached. |
5 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+). |
| identical protein binding | Binding to an identical protein or proteins. |
| protein-macromolecule adaptor activity | The binding activity of a protein that brings together two or more macromolecules in contact, permitting those molecules to function in a coordinated way. The adaptor can bring together two proteins, or a protein and another macromolecule such as a lipid or a nucleic acid. |
| 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. |
21 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. |
| bone morphogenesis | The process in which bones are generated and organized. |
| 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. |
| muscle contraction | A process in which force is generated within muscle tissue, resulting in a change in muscle geometry. Force generation involves a chemo-mechanical energy conversion step that is carried out by the actin/myosin complex activity, which generates force through ATP hydrolysis. |
| negative regulation of calcineurin-NFAT signaling cascade | Any process that stops, prevents, or reduces the frequency, rate or extent of the calcineurin-NFAT signaling cascade. |
| negative regulation of cold-induced thermogenesis | Any process that stops, prevents, or reduces the rate of cold-induced thermogenesis. |
| negative regulation of glycolytic process | Any process that stops, prevents, or reduces the frequency, rate or extent of glycolysis. |
| negative regulation of oxidative phosphorylation | Any process that decreases the frequency, rate or extent of the chemical reactions and pathways resulting in the phosphorylation of ADP to ATP that accompanies the oxidation of a metabolite through the operation of the respiratory chain. Oxidation of compounds establishes a proton gradient across the membrane, providing the energy for ATP synthesis. |
| negative regulation of relaxation of muscle | Any process that stops, prevents or reduces the frequency, rate or extent of relaxation of muscle. |
| positive regulation of bone mineralization involved in bone maturation | Any process that activates or increases the frequency, rate or extent of bone mineralization involved in bone maturation. |
| positive regulation of fast-twitch skeletal muscle fiber contraction | Any process that activates or increases the frequency, rate or extent of fast-twitch skeletal muscle contraction. |
| positive regulation of glucose catabolic process to lactate via pyruvate | Any process that activates or increases the frequency, rate or extent of glucose catabolic process to lactate via pyruvate. |
| positive regulation of skeletal muscle fiber development | Any process that activates, maintains or increases the rate of skeletal muscle fiber development. Muscle fibers are formed by the maturation of myotubes. They can be classed as slow, intermediate/fast or fast. |
| positive regulation of skeletal muscle tissue growth | Any process that activates, maintains or increases the rate of skeletal muscle growth. |
| regulation of aerobic respiration | Any process that modulates the frequency, rate or extent of aerobic respiration. |
| regulation of muscle system process | Any process that modulates the frequency, rate or extent of a muscle system process, a multicellular organismal process carried out by any of the organs or tissues in a muscle system. |
| regulation of the force of skeletal muscle contraction | Any process that modulates the frequency, rate or extent of the force of skeletal muscle contraction. The force of skeletal muscle contraction is produced by acto-myosin interaction processes through the formation of cross bridges. |
| response to denervation involved in regulation of muscle adaptation | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a denervation stimulus. This process occurs as part of the regulation of muscle adaptation. |
| skeletal muscle atrophy | A process, occurring in skeletal muscle, that is characterized by a decrease in protein content, fiber diameter, force production and fatigue resistance in response to different conditions such as starvation, aging and disuse. |
| transition between fast and slow fiber | The process of conversion of fast-contracting muscle fibers to a slower character. This may involve slowing of contractile rate, slow myosin gene induction, increase in oxidative metabolic properties, altered electrophysiology and altered innervation. This process also regulates skeletal muscle adapatation. |
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 |
| Q90734 | ACTN4 | Alpha-actinin-4 | Gallus gallus (Chicken) | SS |
| P05094 | ACTN1 | Alpha-actinin-1 | Gallus gallus (Chicken) | SS |
| P20111 | ACTN2 | Alpha-actinin-2 | Gallus gallus (Chicken) | SS |
| P18091 | Actn | Alpha-actinin, sarcomeric | Drosophila melanogaster (Fruit fly) | SS |
| O43707 | ACTN4 | Alpha-actinin-4 | Homo sapiens (Human) | SS |
| P12814 | ACTN1 | Alpha-actinin-1 | Homo sapiens (Human) | SS |
| P35609 | ACTN2 | Alpha-actinin-2 | Homo sapiens (Human) | EV |
| Q08043 | ACTN3 | Alpha-actinin-3 | Homo sapiens (Human) | SS |
| P57780 | Actn4 | Alpha-actinin-4 | 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 |
| MMMVMQPEGL | GAGEGPFSGG | GGGEYMEQEE | DWDRDLLLDP | AWEKQQRKTF | TAWCNSHLRK |
| 70 | 80 | 90 | 100 | 110 | 120 |
| AGTQIENIEE | DFRNGLKLML | LLEVISGERL | PRPDKGKMRF | HKIANVNKAL | DFIASKGVKL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| VSIGAEEIVD | GNLKMTLGMI | WTIILRFAIQ | DISVEETSAK | EGLLLWCQRK | TAPYRNVNVQ |
| 190 | 200 | 210 | 220 | 230 | 240 |
| NFHTSWKDGL | ALCALIHRHR | PDLIDYAKLR | KDDPIGNLNT | AFEVAEKYLD | IPKMLDAEDI |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VNTPKPDEKA | IMTYVSCFYH | AFAGAEQAET | AANRICKVLA | VNQENEKLME | EYEKLASELL |
| 310 | 320 | 330 | 340 | 350 | 360 |
| EWIRRTVPWL | ENRVGEPSMS | AMQRKLEDFR | DYRRLHKPPR | VQEKCQLEIN | FNTLQTKLRL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| SHRPAFMPSE | GKLVSDIANA | WRGLEQVEKG | YEDWLLSEIR | RLQRLQHLAE | KFQQKASLHE |
| 430 | 440 | 450 | 460 | 470 | 480 |
| AWTRGKEEML | NQHDYESASL | QEVRALLRRH | EAFESDLAAH | QDRVEHIAAL | AQELNELDYH |
| 490 | 500 | 510 | 520 | 530 | 540 |
| EAASVNSRCQ | AICDQWDNLG | TLTQKRRDAL | ERMEKLLETI | DQLQLEFARR | AAPFNNWLDG |
| 550 | 560 | 570 | 580 | 590 | 600 |
| AIEDLQDVWL | VHSVEETQSL | LTAHEQFKAT | LPEADRERGA | ILGIQGEIQK | ICQTYGLRPK |
| 610 | 620 | 630 | 640 | 650 | 660 |
| SGNPYITLSS | QDINNKWDTV | RKLVPSRDQT | LQEELARQQV | NERLRRQFAA | QANAIGPWIQ |
| 670 | 680 | 690 | 700 | 710 | 720 |
| GKVEEVGRLA | AGLAGSLEEQ | MAGLRQQEQN | IINYKSNIDR | LEGDHQLLQE | SLVFDNKHTV |
| 730 | 740 | 750 | 760 | 770 | 780 |
| YSMEHIRVGW | EQLLTSIART | INEVENQVLT | RDAKGLSQEQ | LNEFRASFNH | FDRKRNGMME |
| 790 | 800 | 810 | 820 | 830 | 840 |
| PDDFRACLIS | MGYDLGEVEF | ARIMTMVDPN | AAGVVTFQAF | IDFMTRETAE | TDTAEQVVAS |
| 850 | 860 | 870 | 880 | 890 | |
| FKILAGDKNY | ITPEELRREL | PAEQAEYCIR | RMAPYKGSGA | PSGALDYVAF | SSALYGESDL |