P09327 (VILI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Villin-1

Gene names

Name:	VIL1
Synonyms:	VIL

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	827 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	Epithelial cell-specific Ca2+-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination. Ref.5 Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19
Subunit structure	Monomer. Homodimer; homodimerization is necessary for actin-bundling. Associates with F-actin; phosphorylation at tyrosines residues decreases the association with F-actin. Interacts (phosphorylated at C-terminus tyrosine phosphorylation sites) with PLCG1 (via the SH2 domains). Interacts (phosphorylated form) with PLCG1; the interaction is enhanced by hepatocyte growth factor (HGF) By similarity. Ref.9 Ref.13 Ref.14 Ref.15 Ref.19
Subcellular location	Cytoplasm › cytoskeleton. Cell projection › lamellipodium. Cell projection › ruffle. Cell projection › microvillus. Cell projection › filopodium tip By similarity. Cell projection › filopodium By similarity. Note: Relocalized in the tip of cellular protrusions and filipodial extensions upon infection with S.flexneri in primary intestinal epithelial cells (IEC) and in the tail-like structures forming the actin comets of S.flexneri. Redistributed to the leading edge of hepatocyte growth factor (HGF)-induced lamellipodia By similarity. Rapidly redistributed to ruffles and lamellipodia structures in response to autotaxin, lysophosphatidic acid (LPA) and epidermal growth factor (EGF) treatment. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19
Tissue specificity	Specifically expressed in epithelial cells. Major component of microvilli of intestinal epithelial cells and kidney proximal tubule cells. Expressed in canalicular microvilli of hepatocytes (at protein level). Ref.4 Ref.8
Domain	Consists of a large core fragment in the N-terminal portion and a small headpiece (HP) in the C-terminal portion. The core fragment is necessary for both actin-nucleating and -severing activities, whereas the HP binds F-actin strongly in both the presence and absence of calcium and is necessary in actin-bundling activity. The Gelsolin-like 1 repeat is necessary for the actin-capping activity. The entire core fragment is necessary for the actin-severing activity. Two major calcium-sensitive sites are involved in conformational changes and determine separate functional properties: the first site (Glu-25, Asp-44 and Glu-74) regulates the actin-capping and actin-severing activities; while the second site (Asp-61, Asp-86 and Ala-93) regulates only the actin-severing activity.
Post-translational modification	Tyrosine phosphorylation is induced by epidermal growth factor (EGF) and stimulates cell migration By similarity. Phosphorylated on tyrosine residues by SRC. The unphosphorylated form increases the initial rate of actin-nucleating activity, whereas the tyrosine-phosphorlyated form inhibits actin-nucleating activity, enhances actin-bundling activity and enhances actin-severing activity by reducing high Ca2+ requirements. The tyrosine-phosphorlyated form does not regulate actin-capping activity. Tyrosine phosphorylation is essential for cell migration: tyrosine phosphorylation sites in the N-terminus half regulate actin reorganization and cell morphology, whereas tyrosine phosphorylation sites in the C-terminus half regulate cell migration via interaction with PLCG1. Ref.6 Ref.7 Ref.13 Ref.14
Involvement in disease	Biliary atresia is a chronic and progressive cholestatic liver disease of chilhood characterized by an abnormal villin gene expression and severe malformation of canalicular microvillus structure.
Sequence similarities	Belongs to the villin/gelsolin family. Contains 6 gelsolin-like repeats. Contains 1 HP (headpiece) domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Actin-binding Calcium
Molecular function	Actin capping
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	actin filament capping Inferred from direct assay Ref.13Ref.16Ref.19. Source: UniProtKB actin filament depolymerization Inferred from direct assay Ref.6. Source: UniProtKB actin filament polymerization Inferred from direct assay Ref.6. Source: UniProtKB actin filament severing Inferred from direct assay Ref.13Ref.16Ref.19. Source: UniProtKB cellular response to epidermal growth factor stimulus Inferred from direct assay Ref.14. Source: UniProtKB cellular response to hepatocyte growth factor stimulus Inferred from electronic annotation. Source: Compara cytoplasmic actin-based contraction involved in cell motility Inferred from direct assay Ref.12. Source: UniProtKB epidermal growth factor receptor signaling pathway Inferred from direct assay Ref.14. Source: UniProtKB positive regulation of actin filament bundle assembly Inferred from direct assay Ref.19. Source: UniProtKB positive regulation of epithelial cell migration Inferred from direct assay Ref.14. Source: UniProtKB regulation of actin nucleation Inferred from direct assay Ref.13Ref.16Ref.19. Source: UniProtKB regulation of cell shape Inferred from direct assay Ref.13. Source: UniProtKB regulation of lamellipodium morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB regulation of wound healing Inferred from sequence or structural similarity. Source: UniProtKB response to bacterium Inferred from direct assay Ref.16. Source: UniProtKB
Cellular_component	actin filament bundle Inferred from direct assay Ref.16. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW filopodium tip Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium Inferred from direct assay Ref.13Ref.14Ref.15. Source: UniProtKB microvillus Inferred from direct assay Ref.16. Source: UniProtKB ruffle Inferred from direct assay Ref.12Ref.14Ref.15. Source: UniProtKB
Molecular_function	actin filament binding Inferred from direct assay Ref.6Ref.21Ref.19. Source: UniProtKB calcium ion binding Inferred from direct assay Ref.6. Source: UniProtKB cysteine-type endopeptidase inhibitor activity involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB lysophosphatidic acid binding Inferred from direct assay Ref.19. Source: UniProtKB phosphatidylinositol-4,5-bisphosphate binding Inferred from direct assay Ref.9. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.15. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		9	EBI-1047253,EBI-1047253
PLCG1	P19174	5	EBI-1047253,EBI-79387

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.1

Chain

2 – 827

826

Villin-1

PRO_0000218727

Regions

Repeat

27 – 76

50

Gelsolin-like 1

Repeat

148 – 188

41

Gelsolin-like 2

Repeat

265 – 309

45

Gelsolin-like 3

Repeat

407 – 457

51

Gelsolin-like 4

Repeat

528 – 568

41

Gelsolin-like 5

Repeat

631 – 672

42

Gelsolin-like 6

Domain

761 – 827

67

HP

Region

2 – 734

733

Core

Region

2 – 126

125

Necessary for homodimerization

Region

112 – 119

8

LPA/PIP2-binding site 1

Region

138 – 146

9

LPA/PIP2-binding site 2

Region

735 – 827

93

Headpiece

Region

816 – 824

9

LPA/PIP2-binding site 3

Natural variations

Natural variant

254

1

K → R.
Corresponds to variant rs35305540 [ dbSNP | Ensembl ].

VAR_054502

Experimental info

Mutagenesis

25

1

E → Q: Inhibits activities regarding actin capping, actin severing and actin bundling. Ref.11

Mutagenesis

44

1

D → L: Inhibits activities regarding actin capping and actin severing. Ref.11

Mutagenesis

46

1

Y → F: Reduces activities regarding actin capping and actin severing. Does not reduce lamellipodium or ruffle localization and cell migration. Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-60; F-81; F-256; F-286; F-324; F-461; F-555; F-604 and F-725. Inhibits lamellipodia localization but does not reduce interaction with PLCG1; when associated with F-60; F-81 and F-256. Ref.7 Ref.12 Ref.13 Ref.14 Ref.17

Mutagenesis

60

1

Y → F: Reduces activities regarding actin capping and actin severing, lamellipodium or ruffle localization and cell migration. Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-46; F-81; F-256; F-286; F-324; F-461; F-555; F-604 and F-725. Inhibits lamellipodia localization but does not reduce interaction with PLCG1; when associated with F-46; F-81 and F-256. Ref.7 Ref.12 Ref.13 Ref.14 Ref.17

Mutagenesis

61

1

D → N: Inhibits actin-severing activity. Does not inhibit actin-nucleation and actin-capping activities. Ref.11 Ref.16

Mutagenesis

74

1

E → L: Inhibits activities regarding actin capping and actin severing. Ref.11 Ref.16

Mutagenesis

81

1

Y → F: Reduces activities regarding actin nucleating and actin severing, lamellipodium or ruffle localization and cell migration. Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-46; F-60; F-256; F-286; F-324; F-461; F-555; F-604 and F-725. Inhibits lamellipodia localization but does not reduce interaction with PLCG1; when associated with F-46; F-60 and F-256. Ref.7 Ref.12 Ref.13 Ref.14 Ref.17

Mutagenesis

86 – 91

6

DDFLKG → NTLLKE: Inhibits actin-severing activity and motility of the S.flexneri, does not inhibit activities regarding actin nucleation, actin capping and actin bundling, lamellipodium or ruffle localization and cell morphology; when associated with 125-A--S-129. Ref.11 Ref.16

Mutagenesis

86

1

D → L: Inhibits actin-severing activity. Does not inhibit actin-capping activity. Ref.11

Mutagenesis

93

1

A → G: Inhibits actin-severing activity. Does not inhibit actin-capping activity. Ref.11

Mutagenesis

125 – 129

5

GMKHV → AMHKTS: Inhibits actin-severing activity and motility of the S.flexneri, does not inhibit activities regarding actin nucleation, actin capping and actin bundling, lamellipodium or ruffle localization and cell morphology; when associated with 86-N--E-91. Ref.16

Mutagenesis

138

1

R → A: Reduces binding to PIP2. Ref.9

Mutagenesis

145

1

K → A: Does not reduce binding to PIP2. Ref.9

Mutagenesis

146

1

R → A: Does not reduce binding to PIP2. Ref.9

Mutagenesis

256

1

Y → F: Reduces activities regarding actin nucleation and actin severing, lamellipodium or ruffle localization and cell migration. Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-46; F-60; F-81; F-286; F-324; F-461; F-555; F-604 and F-725. Inhibits lamellipodia localization but does not reduce interaction with PLCG1; when associated with F-46; F-60 and F-81. Ref.7 Ref.12 Ref.13 Ref.14 Ref.17

Mutagenesis

286

1

Y → F: Reduces actin-severing activity and interaction with PLCG1. Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-46; F-60; F-81; F-256; F-324; F-461; F-555; F-604 and F-725. Inhibits interaction with PLCG1 and lamellipodia localization; when associated with F-324; F-461; F-555; F-604 and F-725. Ref.13 Ref.14 Ref.17

Mutagenesis

324

1

Y → F: Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-46; F-60; F-81; F-256; F-286; F-461; F-555; F-604 and F-725. Inhibits interaction with PLCG1 and lamellipodia localization; when associated with F-286; F-461; F-555; F-604 and F-725. Ref.13 Ref.14 Ref.17

Mutagenesis

461

1

Y → F: Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-46; F-60; F-81; F-256; F-286; F-324; F-555; F-604 and F-725. Inhibits interaction with PLCG1 and lamellipodia localization; when associated with F-286; F-324; F-555; F-604 and F-725. Ref.13 Ref.14 Ref.17

Mutagenesis

467

1

D → L: Reduces the Ca(2+)-dependent actin-severing activity. Ref.10

Mutagenesis

555

1

Y → F: Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-46; F-60; F-81; F-256; F-286; F-324; F-461; F-604 and F-725. Inhibits interaction with PLCG1 and lamellipodia localization; when associated with F-286; F-324; F-461; F-604 and F-725. Ref.13 Ref.14 Ref.17

Mutagenesis

604

1

Y → F: Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-46; F-60; F-81; F-256; F-286; F-324; F-461; F-555 and F-725. Inhibits interaction with PLCG1 and lamellipodia localization; when associated with F-286; F-324; F-461; F-555 and F-725. Ref.13 Ref.14 Ref.17

Mutagenesis

715

1

D → L: Reduces the Ca(2+)-dependent actin-severing activity. Ref.10

Mutagenesis

725

1

Y → F: Complete loss of phosphorylation and interaction with PLCG1, does not reduce lamellipodium or ruffle localization, inhibits cell migration; when associated with F-46; F-60; F-81; F-256; F-286; F-324; F-461; F-555 and F-604. Inhibits interaction with PLCG1 and lamellipodia localization; when associated with F-286; F-324; F-461; F-555 and F-604. Ref.13 Ref.14 Ref.17

Mutagenesis

815

1

W → A: Reduces interaction with F-actin. Ref.21

Mutagenesis

822

1

K → A: Does not reduce binding to PIP2. Ref.9

Mutagenesis

824

1

K → A: Does not reduce binding to PIP2. Ref.9

Sequence conflict

146

1

R → K in BAG36454. Ref.2

Sequence conflict

732

1

L → S in CAA31386. Ref.1

Sequence conflict

732

1

L → S in CAA28355. Ref.4

Sequence conflict

735

1

S → L in CAA31386. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

827

Helix Strand Turn

Details...

Beta strand

620 – 625

6

Beta strand

632 – 635

4

Helix

641 – 643

3

Beta strand

648 – 653

6

Beta strand

658 – 662

5

Helix

668 – 684

17

Beta strand

685 – 688

4

Beta strand

695 – 699

5

Helix

705 – 708

4

Helix

795 – 800

6

Helix

806 – 811

6

Helix

814 – 823

10

Sequences

	Sequence		Length	Mass (Da)
	P09327 [UniParc]. Last modified March 3, 2009. Version 4. Checksum: 96439B33B81E5F19	FASTA	827	92,695
	10 20 30 40 50 60 MTKLSAQVKG SLNITTPGLQ IWRIEAMQMV PVPSSTFGSF FDGDCYIILA IHKTASSLSY 70 80 90 100 110 120 DIHYWIGQDS SLDEQGAAAI YTTQMDDFLK GRAVQHREVQ GNESEAFRGY FKQGLVIRKG 130 140 150 160 170 180 GVASGMKHVE TNSYDVQRLL HVKGKRNVVA GEVEMSWKSF NRGDVFLLDL GKLIIQWNGP 190 200 210 220 230 240 ESTRMERLRG MTLAKEIRDQ ERGGRTYVGV VDGENELASP KLMEVMNHVL GKRRELKAAV 250 260 270 280 290 300 PDTVVEPALK AALKLYHVSD SEGNLVVREV ATRPLTQDLL SHEDCYILDQ GGLKIYVWKG 310 320 330 340 350 360 KKANEQEKKG AMSHALNFIK AKQYPPSTQV EVQNDGAESA VFQQLFQKWT ASNRTSGLGK 370 380 390 400 410 420 THTVGSVAKV EQVKFDATSM HVKPQVAAQQ KMVDDGSGEV QVWRIENLEL VPVDSKWLGH 430 440 450 460 470 480 FYGGDCYLLL YTYLIGEKQH YLLYVWQGSQ ASQDEITASA YQAVILDQKY NGEPVQIRVP 490 500 510 520 530 540 MGKEPPHLMS IFKGRMVVYQ GGTSRTNNLE TGPSTRLFQV QGTGANNTKA FEVPARANFL 550 560 570 580 590 600 NSNDVFVLKT QSCCYLWCGK GCSGDEREMA KMVADTISRT EKQVVVEGQE PANFWMALGG 610 620 630 640 650 660 KAPYANTKRL QEENLVITPR LFECSNKTGR FLATEIPDFN QDDLEEDDVF LLDVWDQVFF 670 680 690 700 710 720 WIGKHANEEE KKAAATTAQE YLKTHPSGRD PETPIIVVKQ GHEPPTFTGW FLAWDPFKWS 730 740 750 760 770 780 NTKSYEDLKA ELGNSRDWSQ ITAEVTSPKV DVFNANSNLS SGPLPIFPLE QLVNKPVEEL 790 800 810 820 PEGVDPSRKE EHLSIEDFTQ AFGMTPAAFS ALPRWKQQNL KKEKGLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of human villin: a large duplicated domain homologous with other actin-severing proteins and a unique small carboxy-terminal domain related to villin specificity." Arpin M., Pringault E., Finidori J., Garcia A., Jeltsch J.-M., Louvard D., van de Kerckhove B. J. Cell Biol. 107:1759-1766(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-13. Tissue: Intestine.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"A human villin cDNA clone to investigate the differentiation of intestinal and kidney cells in vivo and in culture." Pringault E., Arpin M., Garcia A., Finidori J., Louvard D. EMBO J. 5:3119-3124(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 718-827, TISSUE SPECIFICITY.
[5]	"Different calcium dependence of the capping and cutting activities of villin." Northrop J., Weber A., Mooseker M.S., Franzini-Armstrong C., Bishop M.F., Dubyak G.R., Tucker M., Walsh T.P. J. Biol. Chem. 261:9274-9281(1986) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Tyrosine phosphorylation of villin regulates the organization of the actin cytoskeleton." Zhai L., Zhao P., Panebra A., Guerrerio A.L., Khurana S. J. Biol. Chem. 276:36163-36167(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ASSOCIATION WITH F-ACTIN, PHOSPHORYLATION.
[7]	"Regulation of actin dynamics by tyrosine phosphorylation: identification of tyrosine phosphorylation sites within the actin-severing domain of villin." Zhai L., Kumar N., Panebra A., Zhao P., Parrill A.L., Khurana S. Biochemistry 41:11750-11760(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY SRC, PHOSPHORYLATION AT TYROSINE RESIDUES, MUTAGENESIS OF TYR-46; TYR-60; TYR-81 AND TYR-256.
[8]	"Abnormalities in villin gene expression and canalicular microvillus structure in progressive cholestatic liver disease of childhood." Phillips M.J., Azuma T., Meredith S.L., Squire J.A., Ackerley C.A., Pluthero F.G., Roberts E.A., Superina R.A., Levy G.A., Marsden P.A. Lancet 362:1112-1119(2003) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN BILIARY ATRESIA, TISSUE SPECIFICITY.
[9]	"Association of villin with phosphatidylinositol 4,5-bisphosphate regulates the actin cytoskeleton." Kumar N., Zhao P., Tomar A., Galea C.A., Khurana S. J. Biol. Chem. 279:3096-3110(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PHOSPHATIDYLINOSITOL, MUTAGENESIS OF ARG-138; LYS-145; ARG-146; LYS-822 AND LYS-824.
[10]	"Identification of a functional switch for actin severing by cytoskeletal proteins." Kumar N., Khurana S. J. Biol. Chem. 279:24915-24918(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-467 AND ASP-715.
[11]	"Functional dissection and molecular characterization of calcium-sensitive actin-capping and actin-depolymerizing sites in villin." Kumar N., Tomar A., Parrill A.L., Khurana S. J. Biol. Chem. 279:45036-45046(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CALCIUM-BINDING, MUTAGENESIS OF GLU-25; ASP-44; ASP-61; GLU-74; ASP-86 AND ALA-93.
[12]	"Regulation of cell motility by tyrosine phosphorylated villin." Tomar A., Wang Y., Kumar N., George S., Ceacareanu B., Hassid A., Chapman K.E., Aryal A.M., Waters C.M., Khurana S. Mol. Biol. Cell 15:4807-4817(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-46; TYR-60; TYR-81 AND TYR-256, SUBCELLULAR LOCATION.
[13]	"Interaction of phospholipase C-gamma1 with villin regulates epithelial cell migration." Tomar A., George S., Kansal P., Wang Y., Khurana S. J. Biol. Chem. 281:31972-31986(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PLCG1, PHOSPHORYLATION AT TYROSINE RESIDUES, MUTAGENESIS OF TYR-46; TYR-60; TYR-81; TYR-256; TYR-286; TYR-324; TYR-461; TYR-555; TYR-604 AND TYR-725, SUBCELLULAR LOCATION.
[14]	"Obligatory role for phospholipase C-gamma(1) in villin-induced epithelial cell migration." Wang Y., Tomar A., George S.P., Khurana S. Am. J. Physiol. 292:C1775-C1786(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PLCG1, PHOSPHORYLATION AT TYROSINE RESIDUES, MUTAGENESIS OF TYR-46; TYR-60; TYR-81; TYR-256; TYR-286; TYR-324; TYR-461; TYR-555; TYR-604 AND TYR-725, SUBCELLULAR LOCATION.
[15]	"Dimerization and actin-bundling properties of villin and its role in the assembly of epithelial cell brush borders." George S.P., Wang Y., Mathew S., Srinivasan K., Khurana S. J. Biol. Chem. 282:26528-26541(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, HOMODIMERIZATION, SUBCELLULAR LOCATION.
[16]	"Villin severing activity enhances actin-based motility in vivo." Revenu C., Courtois M., Michelot A., Sykes C., Louvard D., Robine S. Mol. Biol. Cell 18:827-838(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-61; GLU-74; 86-ASP--GLY-91 AND 125-GLY--VAL-129, SUBCELLULAR LOCATION.
[17]	"Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by redistribution of the actin modifying protein villin to the developing lamellipodia." Khurana S., Tomar A., George S.P., Wang Y., Siddiqui M.R., Guo H., Tigyi G., Mathew S. Exp. Cell Res. 314:530-542(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-46; TYR-60; TYR-81; TYR-256; TYR-286; TYR-324; TYR-461; TYR-555; TYR-604 AND TYR-725, SUBCELLULAR LOCATION.
[18]	"A novel role for villin in intestinal epithelial cell survival and homeostasis." Wang Y., Srinivasan K., Siddiqui M.R., George S.P., Tomar A., Khurana S. J. Biol. Chem. 283:9454-9464(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[19]	"Differential effects of lysophosphatidic acid and phosphatidylinositol 4,5-bisphosphate on actin dynamics by direct association with the actin-binding protein villin." Tomar A., George S.P., Mathew S., Khurana S. J. Biol. Chem. 284:35278-35282(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH LYSOPHOSPHATIDIC ACID, ASSOCIATION WITH F-ACTIN, SUBCELLULAR LOCATION.
[20]	"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].
[21]	"Solution structures of the C-terminal headpiece subdomains of human villin and advillin, evaluation of headpiece F-actin-binding requirements." Vermeulen W., Vanhaesebrouck P., Van Troys M., Verschueren M., Fant F., Goethals M., Ampe C., Martins J.C., Borremans F.A. Protein Sci. 13:1276-1287(2004) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 793-827, ASSOCIATION WITH F-ACTIN, MUTAGENESIS OF TRP-815.
[22]	"Helix straightening as an activation mechanism in the gelsolin superfamily of actin regulatory proteins." Wang H., Chumnarnsilpa S., Loonchanta A., Li Q., Kuan Y.M., Robine S., Larsson M., Mihalek I., Burtnick L.D., Robinson R.C. J. Biol. Chem. 284:21265-21269(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 360-720.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X12901 mRNA. Translation: CAA31386.1.
AK313709 mRNA. Translation: BAG36454.1.
AC073838 Genomic DNA. No translation available.
AC021016 Genomic DNA. No translation available.
X04657 mRNA. Translation: CAA28355.1.

IPI

IPI00218852.

PIR

A31642.

RefSeq

NP_009058.2. NM_007127.2.

UniGene

Hs.654595.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UNC	NMR	-	A	793-827	[»]
3FG7	X-ray	2.00	A/B	360-720	[»]

ProteinModelPortal

P09327.

ModBase

Search...

Protein-protein interaction databases

IntAct

P09327. 1 interaction.

MINT

MINT-1484088.

STRING

9606.ENSP00000248444.

PTM databases

PhosphoSite

P09327.

Polymorphism databases

DMDM

224471905.

Proteomic databases

PaxDb

P09327.

PRIDE

P09327.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000248444; ENSP00000248444; ENSG00000127831.

GeneID

7429.

KEGG

hsa:7429.

UCSC

uc002via.3. human.

Organism-specific databases

CTD

7429.

GeneCards

GC02P219285.

HGNC

HGNC:12690. VIL1.

HPA

CAB002452.
HPA006884.
HPA006885.

MIM

193040. gene.

neXtProt

NX_P09327.

PharmGKB

PA37309.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG304849.

HOGENOM

HOG000233630.

HOVERGEN

HBG004183.

InParanoid

P09327.

KO

K05761.

OMA

KFDATSM.

OrthoDB

EOG45X7VG.

PhylomeDB

P09327.

Gene expression databases

ArrayExpress

P09327.

Bgee

P09327.

CleanEx

HS_VIL1.

Genevestigator

P09327.

GermOnline

ENSG00000127831. Homo sapiens.

Family and domain databases

Gene3D

1.10.950.10. 1 hit.

InterPro

IPR007123. Gelsolin_dom.
IPR015627. Villin.
IPR007122. Villin/Gelsolin.
IPR003128. Villin_headpiece.
[Graphical view]

PANTHER

PTHR11977. PTHR11977. 1 hit.
PTHR11977:SF15. PTHR11977:SF15. 1 hit.

Pfam

PF00626. Gelsolin. 6 hits.
PF02209. VHP. 1 hit.
[Graphical view]

PRINTS

PR00597. GELSOLIN.

SMART

SM00262. GEL. 6 hits.
SM00153. VHP. 1 hit.
[Graphical view]

SUPFAM

SSF47050. VHP. 1 hit.

PROSITE

PS51089. HP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P09327.

GenomeRNAi

7429.

NextBio

29096.

SOURCE

Search...

Entry information

Entry name

VILI_HUMAN

Accession

Primary (citable) accession number: P09327
Secondary accession number(s): B2R9A7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	March 3, 2009
Last modified:	May 1, 2013
This is version 135 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.