Descriptions

Vinculin is a highly conserved intracellular protein with a crucial role in the maintenance and regulation of cell adhesion and migration. N-terminal globular head (Vh) is composed of subdomains (D1-D4). The C-terminal tail (Vt) binds F-actin. A strap sequence (878-890) between Pro-rich region and Vt packs against the Vt and thereby masks the F-actin-binding domain in Vt.

Autoinhibitory domains (AIDs)

Target domain

896-1066 (Vt domain)

Relief mechanism

Ligand binding

Assay

Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

16 structures for P12003

Entry ID Method Resolution Chain Position Source
1QKR X-ray 180 A A/B 879-1135 PDB
1ST6 X-ray 310 A A 1-1135 PDB
1T01 X-ray 206 A A 1-254 PDB
1U6H X-ray 238 A A 1-259 PDB
1XWJ X-ray 260 A A 2-259 PDB
1ZVZ X-ray 180 A A 2-259 PDB
1ZW2 X-ray 210 A A 2-259 PDB
1ZW3 X-ray 330 A A 2-259 PDB
2GDC X-ray 274 A A 1-266 PDB
3JBI EM 850 A V 879-1130 PDB
3ZDL X-ray 230 A A 1-259 PDB
4E17 X-ray 230 A A 1-259 PDB
4E18 X-ray 240 A A 1-259 PDB
6FQ4 X-ray 289 A A 1-259 PDB
6NR7 X-ray 300 A A 1-1135 PDB
AF-P12003-F1 Predicted AlphaFoldDB

20 variants for P12003

Variant ID(s) Position Change Description Diseaes Association Provenance
rs1059717185 3 V>A No Ensembl
rs739133759 39 D>N No Ensembl
rs317315561 318 R>H No Ensembl
rs738602965 402 S>R No Ensembl
rs731452740 540 D>A No Ensembl
rs741660021 551 L>R No Ensembl
rs741207127 602 T>P No Ensembl
rs733694874 604 T>P No Ensembl
rs316607838 612 A>P No Ensembl
rs741437392 682 L>P No Ensembl
rs733879540 683 L>P No Ensembl
rs741323329 848 D>G No Ensembl
rs735779422 920 I>F No Ensembl
rs739957860 928 V>G No Ensembl
rs738211400 933 E>G No Ensembl
rs736113463 934 D>G No Ensembl
rs315952633 942 L>P No Ensembl
rs739496308 951 E>G No Ensembl
rs740517948 1037 V>G No Ensembl
rs731575335 1098 N>T No Ensembl

No associated diseases with P12003

3 regional properties for P12003

Type Name Position InterPro Accession
conserved_site Vinculin, conserved site 162 - 182 IPR000633-1
conserved_site Vinculin, conserved site 277 - 287 IPR000633-2
conserved_site Vinculin, conserved site 497 - 507 IPR000633-3

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Peripheral membrane protein ; Cytoplasmic side
  • Cell junction, adherens junction
  • Cell junction, focal adhesion
  • Cytoplasm, cytoskeleton
  • Cell membrane, sarcolemma ; Peripheral membrane protein ; Cytoplasmic side
  • Cell projection, podosome
  • Recruitment to cell-cell junctions occurs in a myosin II-dependent manner (PubMed:20584916)
  • Interaction with CTNNB1 is necessary for its localization to the cell-cell junctions (PubMed:20086044)
PANTHER Family PTHR46180 VINCULIN
PANTHER Subfamily PTHR46180:SF1 VINCULIN
PANTHER Protein Class
PANTHER Pathway Category Gonadotropin-releasing hormone receptor pathway
Vinculin
Integrin signalling pathway
Vinculin

21 GO annotations of cellular component

Name Definition
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.
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-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.
costamere Regular periodic sub membranous arrays of vinculin in skeletal and cardiac muscle cells, these arrays link Z-discs to the sarcolemma and are associated with links to extracellular matrix.
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).
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.
mitochondrial inner membrane The inner, i.e. lumen-facing, lipid bilayer of the mitochondrial envelope. It is highly folded to form cristae.
muscle tendon junction A cell-substrate junction found at the terminal anchorage site of skeletal muscle cells to tendons.
neuromuscular junction The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential.
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.
podosome An actin-rich adhesion structure characterized by formation upon cell substrate contact and localization at the substrate-attached part of the cell, contain an F-actin-rich core surrounded by a ring structure containing proteins such as vinculin and talin, and have a diameter of 0.5 mm.
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.
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.
skeletal muscle myofibril A myofibril of a skeletal muscle 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.

12 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.
alpha-catenin binding Binding to catenin complex alpha subunit.
beta-catenin binding Binding to a catenin beta subunit.
cadherin binding Binding to cadherin, a type I membrane protein involved in cell adhesion.
dystroglycan binding Binding to dystroglycan, a glycoprotein found in non-muscle tissues as well as in muscle tissues, often in association with dystrophin. The native dystroglycan cleaved into two non-covalently associated subunits, alpha (N-terminal) and beta (C-terminal).
muscle alpha-actinin binding Binding to muscle isoforms of actinin. Muscle alpha-actinin isoforms are found in skeletal and cardiac muscle and are localized to the Z-disc.
protein homodimerization activity Binding to an identical protein to form a homodimer.
scaffold protein binding Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes.
structural molecule activity The action of a molecule that contributes to the structural integrity of a complex or its assembly within or outside a cell.
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.
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.

11 GO annotations of biological process

Name Definition
adherens junction assembly The aggregation, arrangement and bonding together of a set of components to form an adherens junction. An adherens junction is a cell-cell junction composed of the epithelial cadherin-catenin complex at which the cytoplasmic face of the plasma membrane is attached to actin filaments.
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.
axon extension Long distance growth of a single axon process involved in cellular development.
epithelial cell-cell adhesion The attachment of an epithelial cell to another epithelial cell via adhesion molecules.
lamellipodium assembly Formation of a lamellipodium, a thin sheetlike extension of the surface of a migrating cell.
morphogenesis of an epithelium The process in which the anatomical structures of epithelia are generated and organized. An epithelium consists of closely packed cells arranged in one or more layers, that covers the outer surfaces of the body or lines any internal cavity or tube.
protein localization to cell surface A process in which a protein is transported to, or maintained in, a location within the external part of the cell wall and/or plasma membrane.
regulation of cell migration Any process that modulates the frequency, rate or extent of cell migration.
regulation of establishment of endothelial barrier Any process that modulates the frequency, rate or extent of establishment of endothelial barrier.
regulation of focal adhesion assembly Any process that modulates the frequency, rate or extent of focal adhesion formation, the establishment and maturation of focal adhesions.
regulation of protein localization to adherens junction Any process that modulates the frequency, rate or extent of protein localization to adherens junction. An adherens junction is a cell-cell junction composed of the epithelial cadherin-catenin complex at which the cytoplasmic face of the plasma membrane is attached to actin filaments.

16 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q3MHM6 CTNNA1 Catenin alpha-1 Bos taurus (Bovine) SS
P30997 CTNNA2 Catenin alpha-2 Gallus gallus (Chicken) SS
P35220 alpha-Cat Catenin alpha Drosophila melanogaster (Fruit fly) SS
P35221 CTNNA1 Catenin alpha-1 Homo sapiens (Human) EV
P26232 CTNNA2 Catenin alpha-2 Homo sapiens (Human) SS
Q9UI47 CTNNA3 Catenin alpha-3 Homo sapiens (Human) SS
P18206 VCL Vinculin Homo sapiens (Human) SS
P26231 Ctnna1 Catenin alpha-1 Mus musculus (Mouse) EV
Q65CL1 Ctnna3 Catenin alpha-3 Mus musculus (Mouse) EV
Q61301 Ctnna2 Catenin alpha-2 Mus musculus (Mouse) EV
Q64727 Vcl Vinculin Mus musculus (Mouse) SS
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
MPVFHTRTIE SILEPVAQQI SHLVIMHEEG EVDGKAIPDL TAPVSAVQAA VSNLVRVGKE
70 80 90 100 110 120
TVQTTEDQIL KRDMPPAFIK VENACTKLVR AAQMLQADPY SVPARDYLID GSRGILSGTS
130 140 150 160 170 180
DLLLTFDEAE VRKIIRVCKG ILEYLTVAEV VETMEDLVTY TKNLGPGMTK MAKMIDERQQ
190 200 210 220 230 240
ELTHQEHRVM LVNSMNTVKE LLPVLISAMK IFVTTKNTKS QGIEEALKNR NFTVEKMSAE
250 260 270 280 290 300
INEIIRVLQL TSWDEDAWAS KDTEAMKRAL ALIDSKMNQA KGWLRDPNAP PGDAGEQAIR
310 320 330 340 350 360
QILDEAGKAG ELCAGKERRE ILGTCKTLGQ MTDQLADLRA RGQGATPMAM QKAQQVSQGL
370 380 390 400 410 420
DLLTAKVENA ARKLEAMTNS KQAIAKKIDA AQNWLADPNG GSEGEEHIRG IMSEARKVAE
430 440 450 460 470 480
LCEEPKERDD ILRSLGEISA LTAKLSDLRR HGKGDSPEAR ALAKQIATSL QNLQSKTNRA
490 500 510 520 530 540
VANTRPVKAA VHLEGKIEQA QRWIDNPTVD DRGVGQAAIR GLVAEGRRLA NVMMGPYRQD
550 560 570 580 590 600
LLAKCDRVDQ LAAQLADLAA RGEGESPQAR AIAAQLQDSL KDLKARMQEA MTQEVSDVFS
610 620 630 640 650 660
DTTTPIKLLA VAATAPSDTP NREEVFEERA ANFENHAARL GATAEKAAAV GTANKTTVEG
670 680 690 700 710 720
IQATVKSARE LTPQVVSAAR ILLRNPGNQA AYEHFETMKN QWIDNVEKMT GLVDEAIDTK
730 740 750 760 770 780
SLLDASEEAI KKDLDKCKVA MANMQPQMLV AGATSIARRA NRILLVAKRE VENSEDPKFR
790 800 810 820 830 840
EAVKAASDEL SKTISPMVMD AKAVAGNISD PGLQKSFLDS GYRILGAVAK VREAFQPQEP
850 860 870 880 890 900
DFPPPPPDLE HLHLTDELAP PKPPLPEGEV PPPRPPPPEE KDEEFPEQKA GEAINQPMMM
910 920 930 940 950 960
AARQLHDEAR KWSSKPVTVI NEAAEAGVDI DEEDDADVEF SLPSDIEDDY EPELLLMPTN
970 980 990 1000 1010 1020
QPVNQPILAA AQSLHREATK WSSKGNDIIA AAKRMALLMA EMSRLVRGGS GNKRALIQCA
1030 1040 1050 1060 1070 1080
KDIAKASDEV TRLAKEVAKQ CTDKRIRTNL LQVCERIPTI STQLKILSTV KATMLGRTNI
1090 1100 1110 1120 1130
SDEESEQATE MLVHNAQNLM QSVKETVREA EAASIKIRTD AGFTLRWVRK TPWYQ