P26231

EV
Gene name
Ctnna1 (Catna1)
Protein name
Catenin alpha-1
Names
102 kDa cadherin-associated protein, Alpha E-catenin, CAP102
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:12385
EC number
Protein Class
ALPHA CATENIN (PTHR18914)

Descriptions

Alpha-catenin acts as a mechanosensor in adherens junction formation by facilitating the recruitment of vinculin to adherens junctions in the actomyosin-derived tension-dependent manner. Alpha-catenin consists of three major domains with distinct functionalities: an N-terminal (N) domain participates in beta-catenin binding and homodimerization; a modulatory (M) domain interacts with several actin-binding proteins, including vinculin; and a C-terminal (C) domain directly and/or indirectly binds to F-actin. In catenin alpha-1 (Ctnna1, αE-catenin), the vinculin-binding site (VBS) is autoinhibited by occluding the vinculin-binding hydrophobic surfaces within the MI helical bundle. The MIII region inhibits the interaction between the VBS and vinculin. In the high-tension state, Ctnna1 adopts the "open" conformation that disrupts the inhibitory role of MIII region, releasing the MI bundle and unfurling the vinculin-binding site.

Autoinhibitory domains (AIDs)

507-631 (MIII domain) EV

Target domain

305-352 (vinculin-binding site within the MI region)

Relief mechanism

Others

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

11 structures for P26231

Entry ID Method Resolution Chain Position Source
1DOV X-ray 300 A A 82-262 PDB
1DOW X-ray 180 A A 57-261 PDB
1L7C X-ray 250 A A/B/C 385-651 PDB
4E17 X-ray 230 A B 321-356 PDB
4E18 X-ray 240 A B 302-356 PDB
4K1N X-ray 650 A A/B 1-906 PDB
5Y04 X-ray 285 A B 276-375 PDB
6DV1 X-ray 220 A A/B 652-906 PDB
6O3E X-ray 400 A A/B 82-883 PDB
6WVT EM 356 A K/L/N/O/Q/X 671-906 PDB
AF-P26231-F1 Predicted AlphaFoldDB

39 variants for P26231

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389473306 16 K>N No EVA
rs3389487693 36 V>I No EVA
rs3389403527 54 R>H No EVA
rs3389403527 54 R>L No EVA
rs3389452086 56 K>M No EVA
rs3389487719 116 C>Y No EVA
rs3389494555 146 D>V No EVA
rs3389403513 363 A>V No EVA
rs3389494537 369 D>Y No EVA
rs3413041679 399 V>I No EVA
rs3389502416 410 N>K No EVA
rs3389473326 430 L>M No EVA
rs3389485534 432 E>D No EVA
rs3389473382 441 S>Y No EVA
rs3389494552 462 P>L No EVA
rs3389507213 489 E>V No EVA
rs3389494493 493 K>R No EVA
rs3389461571 507 S>P No EVA
rs3389473384 508 I>F No EVA
rs3389502472 510 D>H No EVA
rs3389495701 548 R>W No EVA
rs3389487720 560 M>I No EVA
rs3389452932 625 I>V No EVA
rs3389441276 641 S>Y No EVA
rs3389489164 650 V>I No EVA
rs3408049109 661 D>G No EVA
rs3389495655 676 L>P No EVA
rs3389494478 695 K>R No EVA
rs3389442667 704 K>M No EVA
rs3389502415 717 K>* No EVA
rs3389461539 753 G>* No EVA
rs3508158848 782 R>C No EVA
rs3389489135 785 L>P No EVA
rs3389489119 821 A>V No EVA
rs3389442662 833 V>M No EVA
rs3389473370 838 V>M No EVA
rs3389502428 861 M>L No EVA
rs3389489166 862 K>* No EVA
rs3389487681 863 A>P No EVA

No associated diseases with P26231

No regional properties for P26231

Type Name Position InterPro Accession
No domain, repeats, and functional sites for P26231

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm, cytoskeleton
  • Cell junction, adherens junction
  • Cell membrane ; Peripheral membrane protein ; Cytoplasmic side
  • Cell junction
  • Cytoplasm
  • Nucleus
  • Found at cell-cell boundaries and probably at cell-matrix boundaries
PANTHER Family PTHR18914 ALPHA CATENIN
PANTHER Subfamily PTHR18914:SF24 CATENIN ALPHA-1
PANTHER Protein Class non-motor actin binding protein
PANTHER Pathway Category Alzheimer disease-presenilin pathway
alpha-catenin
Wnt signaling pathway
alpha-catenin
Cadherin signaling pathway
alpha-catenin

12 GO annotations of cellular component

Name Definition
acrosomal vesicle A structure in the head of a spermatozoon that contains acid hydrolases, and is concerned with the breakdown of the outer membrane of the ovum during fertilization. It lies just beneath the plasma membrane and is derived from the lysosome.
actin cytoskeleton The part of the cytoskeleton (the internal framework of a cell) composed of actin and associated proteins. Includes actin cytoskeleton-associated complexes.
adherens junction A cell-cell junction composed of the epithelial cadherin-catenin complex. The epithelial cadherins, or E-cadherins, of each interacting cell extend through the plasma membrane into the extracellular space and bind to each other. The E-cadherins bind to catenins on the cytoplasmic side of the membrane, where the E-cadherin-catenin complex binds to cytoskeletal components and regulatory and signaling molecules.
catenin complex Complex of peripheral cytoplasmic proteins (alpha-, beta- and gamma-catenin) that interact with the cytoplasmic region of uvomorulin/E-cadherin to connect it to the actin cytoskeleton.
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-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.
flotillin complex A protein complex that contains flotillin-1 and flotillin-2, and may contain associated proteins. Flotillins associate into membrane microdomains resembling caveolae.
intercalated disc A complex cell-cell junction at which myofibrils terminate in cardiomyocytes; mediates mechanical and electrochemical integration between individual cardiomyocytes. The intercalated disc contains regions of tight mechanical attachment (fasciae adherentes and desmosomes) and electrical coupling (gap junctions) between adjacent cells.
intracellular membrane-bounded organelle Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes 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.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
zonula adherens A cell-cell adherens junction which forms a continuous belt near the apex of epithelial cells.

8 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.
beta-catenin binding Binding to a catenin beta subunit.
cadherin binding Binding to cadherin, a type I membrane protein involved in cell adhesion.
gamma-catenin binding Binding to catenin complex gamma subunit.
identical protein binding Binding to an identical protein or proteins.
protein-containing complex binding Binding to a macromolecular complex.
structural molecule activity The action of a molecule that contributes to the structural integrity of a complex.
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.

28 GO annotations of biological process

Name Definition
apical junction assembly The formation of an apical junction, a functional unit located near the cell apex at the points of contact between epithelial cells composed of the tight junction, the zonula adherens junction and the desmosomes, by the aggregation, arrangement and bonding together of its constituents.
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
axon regeneration The regrowth of axons following their loss or damage.
cell migration The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues.
cell motility Any process involved in the controlled self-propelled movement of a cell that results in translocation of the cell from one place to another.
cell-cell adhesion The attachment of one cell to another cell via adhesion molecules.
cellular response to indole-3-methanol Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an indole-3-methanol stimulus.
epithelial cell-cell adhesion The attachment of an epithelial cell to another epithelial cell via adhesion molecules.
establishment or maintenance of cell polarity Any cellular process that results in the specification, formation or maintenance of anisotropic intracellular organization or cell growth patterns.
extrinsic apoptotic signaling pathway in absence of ligand The series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with withdrawal of a ligand from a cell surface receptor, and ends when the execution phase of apoptosis is triggered.
gap junction assembly Assembly of gap junctions, which are found in most animal tissues, and serve as direct connections between the cytoplasms of adjacent cells. They provide open channels through the plasma membrane, allowing ions and small molecules (less than approximately a thousand daltons) to diffuse freely between neighboring cells, but preventing the passage of proteins and nucleic acids.
integrin-mediated signaling pathway The series of molecular signals initiated by an extracellular ligand binding to an integrin on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
male gonad development The process whose specific outcome is the progression of the male gonad over time, from its formation to the mature structure.
negative regulation of apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of cell motility Any process that stops, prevents, or reduces the frequency, rate or extent of cell motility.
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Any process that stops, prevents or reduces the frequency, rate or extent of extrinsic apoptotic signaling pathway in absence of ligand.
negative regulation of integrin-mediated signaling pathway Any process that stops, prevents or reduces the frequency, rate or extent of integrin-mediated signaling pathway.
negative regulation of neuroblast proliferation Any process that stops, prevents, or reduces the frequency, rate or extent of the proliferation of neuroblasts.
negative regulation of protein localization to nucleus Any process that stops, prevents or reduces the frequency, rate or extent of protein localization to nucleus.
neuroblast proliferation The expansion of a neuroblast population by cell division. A neuroblast is any cell that will divide and give rise to a neuron.
odontogenesis of dentin-containing tooth The process whose specific outcome is the progression of a dentin-containing tooth over time, from its formation to the mature structure. A dentin-containing tooth is a hard, bony organ borne on the jaw or other bone of a vertebrate, and is composed mainly of dentin, a dense calcified substance, covered by a layer of enamel.
ovarian follicle development The process whose specific outcome is the progression of the ovarian follicle over time, from its formation to the mature structure.
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Any process that activates or increases the frequency, rate or extent of extrinsic apoptotic signaling pathway in absence of ligand.
positive regulation of smoothened signaling pathway Any process that activates or increases the frequency, rate or extent of smoothened signaling.
protein localization Any process in which a protein is transported to, or maintained in, a specific location.
regulation of cell population proliferation Any process that modulates the frequency, rate or extent of cell proliferation.
response to estrogen 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 stimulus by an estrogen, C18 steroid hormones that can stimulate the development of female sexual characteristics.
smoothened signaling pathway The series of molecular signals generated as a consequence of activation of the transmembrane protein Smoothened.

16 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q3MHM6 CTNNA1 Catenin alpha-1 Bos taurus (Bovine) SS
P12003 VCL Vinculin Gallus gallus (Chicken) EV
P30997 CTNNA2 Catenin alpha-2 Gallus gallus (Chicken) SS
P35220 alpha-Cat Catenin alpha Drosophila melanogaster (Fruit fly) SS
P18206 VCL Vinculin Homo sapiens (Human) SS
P26232 CTNNA2 Catenin alpha-2 Homo sapiens (Human) SS
Q9UI47 CTNNA3 Catenin alpha-3 Homo sapiens (Human) SS
P35221 CTNNA1 Catenin alpha-1 Homo sapiens (Human) EV
Q64727 Vcl Vinculin Mus musculus (Mouse) SS
Q65CL1 Ctnna3 Catenin alpha-3 Mus musculus (Mouse) EV
Q61301 Ctnna2 Catenin alpha-2 Mus musculus (Mouse) EV
P26234 VCL Vinculin Sus scrofa (Pig) SS
P85972 Vcl Vinculin Rattus norvegicus (Rat) SS
P90947 hmp-1 Alpha-catenin-like protein hmp-1 Caenorhabditis elegans SS
A4IGI7 ctnna2 Catenin alpha-2 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
B7ZC77 Ctnna2 Catenin alpha-2 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MTAVHAGNIN FKWDPKSLEI RTLAVERLLE PLVTQVTTLV NTNSKGPSNK KRGRSKKAHV
70 80 90 100 110 120
LAASVEQATE NFLEKGDKIA KESQFLKEEL VVAVEDVRKQ GDLMKSAAGE FADDPCSSVK
130 140 150 160 170 180
RGNMVRAARA LLSAVTRLLI LADMADVYKL LVQLKVVEDG ILKLRNAGNE QDLGIQYKAL
190 200 210 220 230 240
KPEVDKLNIM AAKRQQELKD VGNRDQMAAA RGILQKNVPI LYTASQACLQ HPDVAAYKAN
250 260 270 280 290 300
RDLIYKQLQQ AVTGISNAAQ ATASDDAAQH QGGSGGELAY ALNNFDKQII VDPLSFSEER
310 320 330 340 350 360
FRPSLEERLE SIISGAALMA DSSCTRDDRR ERIVAECNAV RQALQDLLSE YMGNAGRKER
370 380 390 400 410 420
SDALNSAIDK MTKKTRDLRR QLRKAVMDHV SDSFLETNVP LLVLIEAAKN GNEKEVKEYA
430 440 450 460 470 480
QVFREHANKL IEVANLACSI SNNEEGVKLV RMSASQLEAL CPQVINAALA LAAKPQSKLA
490 500 510 520 530 540
QENMDLFKEQ WEKQVRVLTD AVDDITSIDD FLAVSENHIL EDVNKCVIAL QEKDVDGLDR
550 560 570 580 590 600
TAGAIRGRAA RVIHVVTSEM DNYEPGVYTE KVLEATKLLS NTVMPRFTEQ VEAAVEALSS
610 620 630 640 650 660
DPAQPMDENE FIDASRLVYD GIRDIRKAVL MIRTPEELDD SDFETEDFDV RSRTSVQTED
670 680 690 700 710 720
DQLIAGQSAR AIMAQLPQEQ KAKIAEQVAS FQEEKSKLDA EVSKWDDSGN DIIVLAKQMC
730 740 750 760 770 780
MIMMEMTDFT RGKGPLKNTS DVISAAKKIA EAGSRMDKLG RTIADHCPDS ACKQDLLAYL
790 800 810 820 830 840
QRIALYCHQL NICSKVKAEV QNLGGELVVS GVDSAMSLIQ AAKNLMNAVV QTVKASYVAS
850 860 870 880 890 900
TKYQKSQGMA SLNLPAVSWK MKAPEKKPLV KREKQDETQT KIKRASQKKH VNPVQALSEF
KAMDSI