P18206 (VINC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vinculin

Alternative name(s):
Metavinculin
Short name=MV

Gene names

Name:

VCL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1134 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. Ref.15 Ref.19
Subunit structure	Exhibits self-association properties. Interacts with APBB1IP, NRAP and SORBS1 By similarity. Interacts with TLN1. Interacts with CTNNB1 and this interaction is necessary for its localization to the cell-cell junctions and for its function in regulating cell surface expression of E-cadherin By similarity. Interacts with SYNM. Ref.11
Subcellular location	Cytoplasm › cytoskeleton. Cell junction › adherens junction. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction › focal adhesion. Note: Cytoplasmic face of adhesion plaques. Recruitment to cell-cell junctions occurs in a myosin II-dependent manner. Interaction with CTNNB1 is necessary for its localization to the cell-cell junctions By similarity. Co-localizes with LIMD1 in the focal adhesions. Ref.12
Tissue specificity	Metavinculin is muscle-specific.
Domain	Exists in at least two conformations. When in the closed, 'inactive' conformation, extensive interactions between the head and tail domains prevent detectable binding to most of its ligands. It takes on an 'active' conformation after cooperative and simultaneous binding of two different ligands. This activation involves displacement of the head-tail interactions and leads to a significant accumulation of ternary complexes. The active form then binds a number of proteins that have both signaling and structural roles that are essential for cell adhesion. Ref.15 The N-terminal globular head (Vh) comprises of subdomains D1-D4. The C-terminal tail (Vt) binds F-actin and cross-links actin filaments into bundles. In isoform 2 (metavinculin) a 68 residue insertion in the tail domain promotes actin severing instead of bundling. An intramolecular interaction between Vh and Vt masks the F-actin-binding domain located in Vt. The binding of talin and alpha-actinin to the D1 subdomain of vinculin induces a helical bundle conversion of this subdomain, leading to the disruption of the intramolecular interaction and the exposure of the cryptic F-actin-binding domain of Vt. Vt inhibits actin filament barbed end elongation without affecting the critical concentration of actin assembly. Ref.15
Post-translational modification	Phosphorylated; on serines, threonines and tyrosines. Phosphorylation on Tyr-1133 in activated platelets affects head-tail interactions and cell spreading but has no effect on actin binding nor on localization to focal adhesion plaques By similarity. Ref.9 Acetylated; mainly by myristic acid but also by a small amount of palmitic acid By similarity.
Involvement in disease	Cardiomyopathy, dilated 1W (CMD1W) [MIM:611407]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.23 Cardiomyopathy, familial hypertrophic 15 (CMH15) [MIM:613255]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.24
Sequence similarities	Belongs to the vinculin/alpha-catenin family.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cardiomyopathy Disease mutation
Domain	Repeat
Ligand	Actin-binding
PTM	Acetylation Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adherens junction assembly Inferred from mutant phenotype PubMed 20086044. Source: BHF-UCL apical junction assembly Inferred from mutant phenotype PubMed 9700171. Source: UniProtKB cell-matrix adhesion Traceable author statement PubMed 20086044. Source: BHF-UCL cellular component movement Traceable author statement PubMed 16130169. Source: UniProtKB epithelial cell-cell adhesion Inferred from mutant phenotype PubMed 20086044. Source: BHF-UCL lamellipodium assembly Inferred from sequence or structural similarity. Source: UniProtKB morphogenesis of an epithelium Inferred from mutant phenotype PubMed 20086044. Source: BHF-UCL muscle contraction Traceable author statement. Source: Reactome negative regulation of cell migration Traceable author statement PubMed 15494027. Source: UniProtKB platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome protein localization to cell surface Inferred from mutant phenotype PubMed 20086044. Source: BHF-UCL
Cellular_component	Z disc Inferred from electronic annotation. Source: Compara actin cytoskeleton Inferred from electronic annotation. Source: InterPro cell-cell adherens junction Inferred from direct assay PubMed 20086044. Source: BHF-UCL costamere Inferred from sequence or structural similarity. Source: UniProtKB cytoskeleton Traceable author statement PubMed 16130169. Source: UniProtKB cytosol Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome fascia adherens Inferred from electronic annotation. Source: Compara focal adhesion Inferred from sequence or structural similarity. Source: UniProtKB protein complex Inferred from direct assay PubMed 9700171. Source: UniProtKB sarcolemma Inferred from electronic annotation. Source: Compara
Molecular_function	actin binding Inferred from direct assay PubMed 16803572. Source: BHF-UCL beta-catenin binding Inferred from sequence or structural similarity PubMed 20086044. Source: BHF-UCL cadherin binding Inferred from sequence or structural similarity PubMed 20086044. Source: BHF-UCL structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: P18206-1)

Also known as: Metavinculin;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: P18206-2)

Also known as: Vinculin;

The sequence of this isoform differs from the canonical sequence as follows:
     916-983: Missing.

Isoform 3 (identifier: P18206-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: Missing.
     262-295: DTEAMKRALASIDSKLNQAKGWLRDPSASPGDAG → VRVLSGEISKIPNSPWLGVLIGTCLILYLVIFVA
     296-1134: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 1134

1133

Vinculin

PRO_0000064252

Regions

Repeat

259 – 369

111

1

Repeat

370 – 479

110

2

Repeat

480 – 589

110

3

Region

2 – 835

834

N-terminal globular head

Region

168 – 208

41

Talin-interaction By similarity

Region

259 – 589

331

3 X 112 AA tandem repeats

Region

836 – 878

43

Linker (Pro-rich)

Region

879 – 1134

256

C-terminal tail

Region

1003 – 1046

44

Facilitates phospholipid membrane insertion By similarity

Region

1120 – 1134

15

Facilitates phospholipid membrane insertion By similarity

Compositional bias

837 – 878

42

Pro-rich

Amino acid modifications

Modified residue

173

1

N6-acetyllysine Ref.14

Modified residue

288

1

Phosphoserine Ref.16

Modified residue

290

1

Phosphoserine Ref.13 Ref.16 Ref.18

Modified residue

324

1

Phosphothreonine By similarity

Modified residue

346

1

Phosphoserine Ref.18

Modified residue

434

1

Phosphoserine Ref.18

Modified residue

496

1

N6-acetyllysine Ref.14

Modified residue

537

1

Phosphotyrosine Potential

Modified residue

721

1

Phosphoserine Ref.10 Ref.13 Ref.16 Ref.18

Modified residue

774

1

Phosphoserine By similarity

Modified residue

822

1

Phosphotyrosine Ref.13

Modified residue

1133

1

Phosphotyrosine; by SRC-type Tyr-kinases Ref.9

Natural variations

Alternative sequence

1 – 73

73

Missing in isoform 3.

VSP_011857

Alternative sequence

262 – 295

34

DTEAM…PGDAG → VRVLSGEISKIPNSPWLGVL IGTCLILYLVIFVA in isoform 3.

VSP_011858

Alternative sequence

296 – 1134

839

Missing in isoform 3.

VSP_011859

Alternative sequence

916 – 983

68

Missing in isoform 1.

VSP_006731

Natural variant

234

1

V → L. Ref.4
Corresponds to variant rs17853882 [ dbSNP | Ensembl ].

VAR_037667

Natural variant

277

1

L → M in CMH15. Ref.24

VAR_035101

Natural variant

934

1

A → V. Ref.23
Corresponds to variant rs16931179 [ dbSNP | Ensembl ].

VAR_035102

Natural variant

943

1

P → A. Ref.23

VAR_035103

Natural variant

954

1

Missing in CMD1W. Ref.22

VAR_035104

Natural variant

975

1

R → W in CMD1W; significantly alters metavinculin-mediated cross-linking of actin filaments. Ref.22 Ref.23

VAR_035105

Secondary structure

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1134

Helix Strand Turn

Details...

Beta strand

4 – 6

3

Helix

7 – 13

7

Helix

16 – 26

11

Beta strand

28 – 30

3

Beta strand

33 – 35

3

Helix

38 – 40

3

Helix

41 – 64

24

Helix

68 – 97

30

Helix

102 – 145

44

Helix

146 – 150

5

Helix

154 – 179

26

Helix

185 – 218

34

Beta strand

220 – 222

3

Helix

223 – 248

26

Helix

253 – 255

3

Helix

258 – 274

17

Helix

277 – 284

8

Helix

294 – 310

17

Helix

315 – 338

24

Turn

339 – 342

4

Helix

343 – 345

3

Helix

347 – 351

5

Helix

353 – 393

41

Turn

394 – 396

3

Helix

402 – 420

19

Helix

425 – 447

23

Turn

448 – 450

3

Turn

455 – 458

4

Helix

460 – 482

23

Helix

493 – 505

13

Helix

514 – 530

17

Helix

535 – 561

27

Helix

568 – 577

10

Helix

579 – 598

20

Helix

604 – 614

11

Turn

620 – 624

5

Helix

625 – 650

26

Helix

655 – 681

27

Helix

690 – 714

25

Helix

719 – 743

25

Helix

746 – 772

27

Helix

777 – 792

16

Helix

794 – 806

13

Turn

811 – 813

3

Helix

814 – 833

20

Helix

896 – 904

9

Helix

964 – 977

14

Helix

986 – 1005

20

Helix

1012 – 1037

26

Helix

1043 – 1053

11

Helix

1056 – 1072

17

Turn

1073 – 1076

4

Beta strand

1077 – 1079

3

Helix

1081 – 1113

33

Beta strand

1114 – 1117

4

Beta strand

1119 – 1121

3

Beta strand

1128 – 1130

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (Metavinculin) [UniParc]. Last modified January 23, 2007. Version 4. Checksum: BFBD687DA836B0FA	FASTA	1,134	123,799
	10 20 30 40 50 60 MPVFHTRTIE SILEPVAQQI SHLVIMHEEG EVDGKAIPDL TAPVAAVQAA VSNLVRVGKE 70 80 90 100 110 120 TVQTTEDQIL KRDMPPAFIK VENACTKLVQ AAQMLQSDPY SVPARDYLID GSRGILSGTS 130 140 150 160 170 180 DLLLTFDEAE VRKIIRVCKG ILEYLTVAEV VETMEDLVTY TKNLGPGMTK MAKMIDERQQ 190 200 210 220 230 240 ELTHQEHRVM LVNSMNTVKE LLPVLISAMK IFVTTKNSKN QGIEEALKNR NFTVEKMSAE 250 260 270 280 290 300 INEIIRVLQL TSWDEDAWAS KDTEAMKRAL ASIDSKLNQA KGWLRDPSAS PGDAGEQAIR 310 320 330 340 350 360 QILDEAGKVG ELCAGKERRE ILGTCKMLGQ MTDQVADLRA RGQGSSPVAM QKAQQVSQGL 370 380 390 400 410 420 DVLTAKVENA ARKLEAMTNS KQSIAKKIDA AQNWLADPNG GPEGEEQIRG ALAEARKIAE 430 440 450 460 470 480 LCDDPKERDD ILRSLGEISA LTSKLADLRR QGKGDSPEAR ALAKQVATAL QNLQTKTNRA 490 500 510 520 530 540 VANSRPAKAA VHLEGKIEQA QRWIDNPTVD DRGVGQAAIR GLVAEGHRLA NVMMGPYRQD 550 560 570 580 590 600 LLAKCDRVDQ LTAQLADLAA RGEGESPQAR ALASQLQDSL KDLKARMQEA MTQEVSDVFS 610 620 630 640 650 660 DTTTPIKLLA VAATAPPDAP NREEVFDERA ANFENHSGKL GATAEKAAAV GTANKSTVEG 670 680 690 700 710 720 IQASVKTARE LTPQVVSAAR ILLRNPGNQA AYEHFETMKN QWIDNVEKMT GLVDEAIDTK 730 740 750 760 770 780 SLLDASEEAI KKDLDKCKVA MANIQPQMLV AGATSIARRA NRILLVAKRE VENSEDPKFR 790 800 810 820 830 840 EAVKAASDEL SKTISPMVMD AKAVAGNISD PGLQKSFLDS GYRILGAVAK VREAFQPQEP 850 860 870 880 890 900 DFPPPPPDLE QLRLTDELAP PKPPLPEGEV PPPRPPPPEE KDEEFPEQKA GEVINQPMMM 910 920 930 940 950 960 AARQLHDEAR KWSSKPGIPA AEVGIGVVAE ADAADAAGFP VPPDMEDDYE PELLLMPSNQ 970 980 990 1000 1010 1020 PVNQPILAAA QSLHREATKW SSKGNDIIAA AKRMALLMAE MSRLVRGGSG TKRALIQCAK 1030 1040 1050 1060 1070 1080 DIAKASDEVT RLAKEVAKQC TDKRIRTNLL QVCERIPTIS TQLKILSTVK ATMLGRTNIS 1090 1100 1110 1120 1130 DEESEQATEM LVHNAQNLMQ SVKETVREAE AASIKIRTDA GFTLRWVRKT PWYQ
	Isoform 1 (Vinculin) [UniParc]. Checksum: C9B67AA072009EBD	FASTA	1,066	116,722
	10 20 30 40 50 60 MPVFHTRTIE SILEPVAQQI SHLVIMHEEG EVDGKAIPDL TAPVAAVQAA VSNLVRVGKE 70 80 90 100 110 120 TVQTTEDQIL KRDMPPAFIK VENACTKLVQ AAQMLQSDPY SVPARDYLID GSRGILSGTS 130 140 150 160 170 180 DLLLTFDEAE VRKIIRVCKG ILEYLTVAEV VETMEDLVTY TKNLGPGMTK MAKMIDERQQ 190 200 210 220 230 240 ELTHQEHRVM LVNSMNTVKE LLPVLISAMK IFVTTKNSKN QGIEEALKNR NFTVEKMSAE 250 260 270 280 290 300 INEIIRVLQL TSWDEDAWAS KDTEAMKRAL ASIDSKLNQA KGWLRDPSAS PGDAGEQAIR 310 320 330 340 350 360 QILDEAGKVG ELCAGKERRE ILGTCKMLGQ MTDQVADLRA RGQGSSPVAM QKAQQVSQGL 370 380 390 400 410 420 DVLTAKVENA ARKLEAMTNS KQSIAKKIDA AQNWLADPNG GPEGEEQIRG ALAEARKIAE 430 440 450 460 470 480 LCDDPKERDD ILRSLGEISA LTSKLADLRR QGKGDSPEAR ALAKQVATAL QNLQTKTNRA 490 500 510 520 530 540 VANSRPAKAA VHLEGKIEQA QRWIDNPTVD DRGVGQAAIR GLVAEGHRLA NVMMGPYRQD 550 560 570 580 590 600 LLAKCDRVDQ LTAQLADLAA RGEGESPQAR ALASQLQDSL KDLKARMQEA MTQEVSDVFS 610 620 630 640 650 660 DTTTPIKLLA VAATAPPDAP NREEVFDERA ANFENHSGKL GATAEKAAAV GTANKSTVEG 670 680 690 700 710 720 IQASVKTARE LTPQVVSAAR ILLRNPGNQA AYEHFETMKN QWIDNVEKMT GLVDEAIDTK 730 740 750 760 770 780 SLLDASEEAI KKDLDKCKVA MANIQPQMLV AGATSIARRA NRILLVAKRE VENSEDPKFR 790 800 810 820 830 840 EAVKAASDEL SKTISPMVMD AKAVAGNISD PGLQKSFLDS GYRILGAVAK VREAFQPQEP 850 860 870 880 890 900 DFPPPPPDLE QLRLTDELAP PKPPLPEGEV PPPRPPPPEE KDEEFPEQKA GEVINQPMMM 910 920 930 940 950 960 AARQLHDEAR KWSSKGNDII AAAKRMALLM AEMSRLVRGG SGTKRALIQC AKDIAKASDE 970 980 990 1000 1010 1020 VTRLAKEVAK QCTDKRIRTN LLQVCERIPT ISTQLKILST VKATMLGRTN ISDEESEQAT 1030 1040 1050 1060 EMLVHNAQNL MQSVKETVRE AEAASIKIRT DAGFTLRWVR KTPWYQ
	Isoform 3 [UniParc]. Checksum: CBC9C4E86C7B5002	FASTA	222	24,904
	10 20 30 40 50 60 MPPAFIKVEN ACTKLVQAAQ MLQSDPYSVP ARDYLIDGSR GILSGTSDLL LTFDEAEVRK 70 80 90 100 110 120 IIRVCKGILE YLTVAEVVET MEDLVTYTKN LGPGMTKMAK MIDERQQELT HQEHRVMLVN 130 140 150 160 170 180 SMNTVKELLP VLISAMKIFV TTKNSKNQGI EEALKNRNFT VEKMSAEINE IIRVLQLTSW 190 200 210 220 DEDAWASKVR VLSGEISKIP NSPWLGVLIG TCLILYLVIF VA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequence of human vinculin and assignment of the gene to chromosome 10." Weller P.A., Ogryzko E.P., Corben E.B., Zhidkova N.I., Patel B., Price G.J., Spurr N.K., Koteliansky V.E., Critchley D.R. Proc. Natl. Acad. Sci. U.S.A. 87:5667-5671(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Endothelial cell.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Retina.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-234. Tissue: Prostate.
[5]	"Organization of the human gene encoding the cytoskeletal protein vinculin and the sequence of the vinculin promoter." Moiseyeva E.P., Weller P.A., Zhidkova N.I., Corben E.B., Patel B., Jasinska I., Koteliansky V.E., Critchley D.R. J. Biol. Chem. 268:4318-4325(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[6]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 114-132; 247-261; 327-339; 353-366; 465-476 AND 548-561, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[7]	"An additional exon in the human vinculin gene specifically encodes meta-vinculin-specific difference peptide. Cross-species comparison reveals variable and conserved motifs in the meta-vinculin insert." Koteliansky V.E., Ogryzko E.P., Zhidkova N.I., Weller P.A., Critchley D.R., Vancompernolle K., Vandekerckhove J., Strasser P., Way M., Gimona M., Small J.V. Eur. J. Biochem. 204:767-772(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 854-1051, ALTERNATIVE SPLICING (ISOFORM 2). Tissue: Uterus.
[8]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-7 (ISOFORMS 1/2). Tissue: Platelet.
[9]	"The phosphorylation of vinculin on tyrosine residues 100 and 1065, mediated by SRC kinases, affects cell spreading." Zhang Z., Izaguirre G., Lin S.-Y., Lee H.Y., Schaefer E., Haimovich B. Mol. Biol. Cell 15:4234-4247(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-1133, MASS SPECTROMETRY.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-721, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Human alpha-synemin interacts directly with vinculin and metavinculin." Sun N., Critchley D.R., Paulin D., Li Z., Robson R.M. Biochem. J. 409:657-667(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SYNM.
[12]	"Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers." Huggins C.J., Andrulis I.L. Cancer Lett. 267:55-66(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-290; SER-721 AND TYR-822, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-173 AND LYS-496, MASS SPECTROMETRY.
[15]	"Vinculin is a dually regulated actin filament barbed end-capping and side-binding protein." Le Clainche C., Dwivedi S.P., Didry D., Carlier M.F. J. Biol. Chem. 285:23420-23432(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DOMAIN.
[16]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-288; SER-290 AND SER-721, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-290; SER-346; SER-434 AND SER-721, MASS SPECTROMETRY.
[19]	"The C-terminal tail domain of metavinculin, vinculin's splice variant, severs actin filaments." Janssen M.E., Liu H., Volkmann N., Hanein D. J. Cell Biol. 197:585-593(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (ISOFORM 2).
[20]	"Structural basis for amplifying vinculin activation by talin." Izard T., Vonrhein C. J. Biol. Chem. 279:27667-27678(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 1-258 IN COMPLEX WITH TLN1.
[21]	"Vinculin activation by talin through helical bundle conversion." Izard T., Evans G., Borgon R.A., Rush C.L., Bricogne G., Bois P.R.J. Nature 427:171-175(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-258 IN COMPLEX WITH TLN1.
[22]	"Metavinculin mutations alter actin interaction in dilated cardiomyopathy." Olson T.M., Illenberger S., Kishimoto N.Y., Huttelmaier S., Keating M.T., Jockusch B.M. Circulation 105:431-437(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CMD1W LEU-954 DEL AND TRP-975, CHARACTERIZATION OF VARIANT CMD1W TRP-975.
[23]	"Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy." Vasile V.C., Will M.L., Ommen S.R., Edwards W.D., Olson T.M., Ackerman M.J. Mol. Genet. Metab. 87:169-174(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMD1W TRP-975, VARIANTS VAL-934 AND ALA-943.
[24]	"A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy." Vasile V.C., Ommen S.R., Edwards W.D., Ackerman M.J. Biochem. Biophys. Res. Commun. 345:998-1003(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMH15 MET-277.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Vinculin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M33308 mRNA. Translation: AAA61283.1.
BX537994 mRNA. Translation: CAD97952.1.
AL596247, AL731576 Genomic DNA. Translation: CAI13972.1.
AL731576, AL596247 Genomic DNA. Translation: CAI39673.1.
BC039174 mRNA. Translation: AAH39174.1.
L04933 Genomic DNA. Translation: AAA61271.1.
S87180, S87175, S87178 Genomic DNA. Translation: AAB21656.1.
S87223, S87218 Genomic DNA. Translation: AAB21657.1.

IPI

IPI00291175.
IPI00307162.
IPI00384973.

PIR

A35955.

RefSeq

NP_003364.1. NM_003373.3.
NP_054706.1. NM_014000.2.

UniGene

Hs.643896.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RKC	X-ray	2.70	A	1-258	[»]
1RKE	X-ray	2.35	A	1-258	[»]
			B	882-1134	[»]
1SYQ	X-ray	2.42	A	1-258	[»]
1TR2	X-ray	2.90	A/B	1-1134	[»]
1YDI	X-ray	1.80	A	1-258	[»]
2GWW	X-ray	2.72	A	1-257	[»]
2HSQ	X-ray	3.97	A	2-257	[»]
2IBF	X-ray	3.20	A	1-258	[»]
3H2U	X-ray	2.75	A/C	879-1134	[»]
3H2V	X-ray	2.90	A/B/C/D	879-1134	[»]
3MYI	X-ray	2.20	A	959-1130	[»]
3RF3	X-ray	1.61	A/B	1-258	[»]
3S90	X-ray	1.97	A/B	1-252	[»]
3TJ5	X-ray	1.99	A	1-255	[»]
3TJ6	X-ray	2.76	A	1-257	[»]
3VF0	X-ray	2.54	A	856-1134	[»]
4DJ9	X-ray	2.25	A	1-258	[»]
4EHP	X-ray	2.66	A	1-252	[»]

ProteinModelPortal

P18206.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35570N.

IntAct

P18206. 11 interactions.

MINT

MINT-92846.

STRING

9606.ENSP00000211998.

PTM databases

PhosphoSite

P18206.

Polymorphism databases

DMDM

21903479.

2D gel databases

DOSAC-COBS-2DPAGE

P18206.

OGP

P18206.

REPRODUCTION-2DPAGE

IPI00291175.

SWISS-2DPAGE

P18206.

UCD-2DPAGE

P18206.

Proteomic databases

PaxDb

P18206.

PRIDE

P18206.

Protocols and materials databases

DNASU

7414.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000211998; ENSP00000211998; ENSG00000035403.
ENST00000372755; ENSP00000361841; ENSG00000035403.

GeneID

7414.

KEGG

hsa:7414.

UCSC

uc001jwd.3. human.
uc001jwe.3. human.

Organism-specific databases

CTD

7414.

GeneCards

GC10P075757.

H-InvDB

HIX0170429.

HGNC

HGNC:12665. VCL.

HPA

CAB002453.
HPA002131.

MIM

193065. gene.
611407. phenotype.
613255. phenotype.

neXtProt

NX_P18206.

Orphanet

154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.

PharmGKB

PA37288.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG329927.

HOGENOM

HOG000007828.

HOVERGEN

HBG079758.

InParanoid

P18206.

KO

K05700.

OMA

ELTHQVH.

OrthoDB

EOG4P5K8C.

PhylomeDB

P18206.

Enzyme and pathway databases

Pathway_Interaction_DB

avb3_integrin_pathway. Integrins in angiogenesis.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.

Reactome

REACT_17044. Muscle contraction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P18206.

Bgee

P18206.

CleanEx

HS_VCL.

Genevestigator

P18206.

GermOnline

ENSG00000035403. Homo sapiens.

Family and domain databases

InterPro

IPR017997. Vinculin.
IPR006077. Vinculin/catenin.
IPR000633. Vinculin_CS.
[Graphical view]

Pfam

PF01044. Vinculin. 3 hits.
[Graphical view]

PRINTS

PR00806. VINCULIN.

SUPFAM

SSF47220. Vinculin/catenin. 8 hits.

PROSITE

PS00663. VINCULIN_1. 1 hit.
PS00664. VINCULIN_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

VCL. human.

EvolutionaryTrace

P18206.

GenomeRNAi

7414.

NextBio

29028.

SOURCE

Search...

Entry information

Entry name

VINC_HUMAN

Accession

Primary (citable) accession number: P18206
Secondary accession number(s): Q16450 , Q5SWX2, Q7Z3B8, Q8IXU7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 155 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.