Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P09327 (VILI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Villin-1
Gene names
Name:VIL1
Synonyms:VIL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length827 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.7 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21

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.11 Ref.15 Ref.16 Ref.17 Ref.21

Subcellular location

Cytoplasmcytoskeleton. Cell projectionlamellipodium. Cell projectionruffle. Cell projectionmicrovillus. Cell projectionfilopodium tip By similarity. Cell projectionfilopodium 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.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21

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.6 Ref.10

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.8 Ref.9 Ref.15 Ref.16

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 processApoptosis
   Cellular componentCell projection
Cytoplasm
Cytoskeleton
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandActin-binding
Calcium
   Molecular functionActin capping
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactin filament capping

Inferred from direct assay Ref.15Ref.18Ref.21. Source: UniProtKB

actin filament depolymerization

Inferred from direct assay Ref.8. Source: UniProtKB

actin filament polymerization

Inferred from direct assay Ref.8. Source: UniProtKB

actin filament severing

Inferred from direct assay Ref.15Ref.18Ref.21. Source: UniProtKB

cellular response to epidermal growth factor stimulus

Inferred from direct assay Ref.16. Source: UniProtKB

cellular response to hepatocyte growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

cytoplasmic actin-based contraction involved in cell motility

Inferred from direct assay Ref.14. Source: UniProtKB

epidermal growth factor receptor signaling pathway

Inferred from direct assay Ref.16. Source: UniProtKB

epithelial cell differentiation

Inferred from expression pattern PubMed 21492153. Source: UniProt

positive regulation of actin filament bundle assembly

Inferred from direct assay Ref.21. Source: UniProtKB

positive regulation of cell migration

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of epithelial cell migration

Inferred from direct assay Ref.16. Source: UniProtKB

protein complex assembly

Traceable author statement Ref.1. Source: ProtInc

regulation of actin nucleation

Inferred from direct assay Ref.15Ref.18Ref.21. Source: UniProtKB

regulation of cell shape

Inferred from direct assay Ref.15. 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.18. Source: UniProtKB

   Cellular_componentactin filament bundle

Inferred from direct assay Ref.18. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

filopodium

Inferred from direct assay Ref.14. Source: UniProtKB

filopodium tip

Inferred from sequence or structural similarity. Source: UniProtKB

lamellipodium

Inferred from direct assay Ref.15Ref.16Ref.17. Source: UniProtKB

microvillus

Inferred from direct assay Ref.18. Source: UniProtKB

ruffle

Inferred from direct assay Ref.14Ref.16Ref.17. Source: UniProtKB

   Molecular_functionactin filament binding

Inferred from direct assay Ref.8Ref.23Ref.21. Source: UniProtKB

calcium ion binding

Inferred from direct assay Ref.8. Source: UniProtKB

cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

identical protein binding

Inferred from physical interaction Ref.17. Source: IntAct

lysophosphatidic acid binding

Inferred from direct assay Ref.21. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate binding

Inferred from direct assay Ref.11. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.16. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.17. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself9EBI-1047253,EBI-1047253
PLCG1P191745EBI-1047253,EBI-79387

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P09327-1)

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 2 (identifier: P09327-2)

The sequence of this isoform differs from the canonical sequence as follows:
     368-421: AKVEQVKFDA...PVDSKWLGHF → GEGQAGAVRE...VLADGDVDKL
     422-827: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.1
Chain2 – 827826Villin-1
PRO_0000218727

Regions

Repeat27 – 7650Gelsolin-like 1
Repeat148 – 18841Gelsolin-like 2
Repeat265 – 30945Gelsolin-like 3
Repeat407 – 45751Gelsolin-like 4
Repeat528 – 56841Gelsolin-like 5
Repeat631 – 67242Gelsolin-like 6
Domain761 – 82767HP
Region2 – 734733Core
Region2 – 126125Necessary for homodimerization
Region112 – 1198LPA/PIP2-binding site 1
Region138 – 1469LPA/PIP2-binding site 2
Region735 – 82793Headpiece
Region816 – 8249LPA/PIP2-binding site 3

Natural variations

Alternative sequence368 – 42154AKVEQ…WLGHF → GEGQAGAVREPGSRSWARRA TWSTTHPPSLTCIFNEDFYA GSGLVLADGDVDKL in isoform 2.
VSP_054436
Alternative sequence422 – 827406Missing in isoform 2.
VSP_054437
Natural variant2541K → R.
Corresponds to variant rs35305540 [ dbSNP | Ensembl ].
VAR_054502

Experimental info

Mutagenesis251E → Q: Inhibits activities regarding actin capping, actin severing and actin bundling. Ref.13
Mutagenesis441D → L: Inhibits activities regarding actin capping and actin severing. Ref.13
Mutagenesis461Y → 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.9 Ref.14 Ref.15 Ref.16 Ref.19
Mutagenesis601Y → 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.9 Ref.14 Ref.15 Ref.16 Ref.19
Mutagenesis611D → N: Inhibits actin-severing activity. Does not inhibit actin-nucleation and actin-capping activities. Ref.13 Ref.18
Mutagenesis741E → L: Inhibits activities regarding actin capping and actin severing. Ref.13 Ref.18
Mutagenesis811Y → 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.9 Ref.14 Ref.15 Ref.16 Ref.19
Mutagenesis86 – 916DDFLKG → 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.13 Ref.18
Mutagenesis861D → L: Inhibits actin-severing activity. Does not inhibit actin-capping activity. Ref.13
Mutagenesis931A → G: Inhibits actin-severing activity. Does not inhibit actin-capping activity. Ref.13
Mutagenesis125 – 1295GMKHV → 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.18
Mutagenesis1381R → A: Reduces binding to PIP2. Ref.11
Mutagenesis1451K → A: Does not reduce binding to PIP2. Ref.11
Mutagenesis1461R → A: Does not reduce binding to PIP2. Ref.11
Mutagenesis2561Y → 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.9 Ref.14 Ref.15 Ref.16 Ref.19
Mutagenesis2861Y → 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.15 Ref.16 Ref.19
Mutagenesis3241Y → 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.15 Ref.16 Ref.19
Mutagenesis4611Y → 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.15 Ref.16 Ref.19
Mutagenesis4671D → L: Reduces the Ca(2+)-dependent actin-severing activity. Ref.12
Mutagenesis5551Y → 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.15 Ref.16 Ref.19
Mutagenesis6041Y → 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.15 Ref.16 Ref.19
Mutagenesis7151D → L: Reduces the Ca(2+)-dependent actin-severing activity. Ref.12
Mutagenesis7251Y → 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.15 Ref.16 Ref.19
Mutagenesis8151W → A: Reduces interaction with F-actin. Ref.23
Mutagenesis8221K → A: Does not reduce binding to PIP2. Ref.11
Mutagenesis8241K → A: Does not reduce binding to PIP2. Ref.11
Sequence conflict1461R → K in BAG36454. Ref.2
Sequence conflict7321L → S in CAA31386. Ref.1
Sequence conflict7321L → S in CAA28355. Ref.4
Sequence conflict7351S → L in CAA31386. Ref.1

Secondary structure

........................ 827
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 3, 2009. Version 4.
Checksum: 96439B33B81E5F19

FASTA82792,695
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 897332F5D0ECFC02
Show »

FASTA42146,567

References

« Hide '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] (ISOFORM 1), 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. expand/collapse author list , 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] (ISOFORM 1).
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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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 2).
Tissue: Liver.
[6]"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 (ISOFORM 1), TISSUE SPECIFICITY.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
[17]"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.
[18]"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.
[19]"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.
[20]"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.
[21]"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.
[22]"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].
[23]"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.
[24]"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.
AC021016 Genomic DNA. No translation available.
AC073838 Genomic DNA. Translation: AAY14886.1.
CH471063 Genomic DNA. Translation: EAW70619.1.
BC017303 mRNA. Translation: AAH17303.1.
X04657 mRNA. Translation: CAA28355.1.
CCDSCCDS2417.1.
PIRA31642.
RefSeqNP_009058.2. NM_007127.2. [P09327-1]
UniGeneHs.654595.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1UNCNMR-A793-827[»]
3FG7X-ray2.00A/B360-720[»]
ProteinModelPortalP09327.
SMRP09327. Positions 3-720, 767-827.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113270. 3 interactions.
IntActP09327. 1 interaction.
MINTMINT-1484088.
STRING9606.ENSP00000248444.

PTM databases

PhosphoSiteP09327.

Polymorphism databases

DMDM224471905.

Proteomic databases

MaxQBP09327.
PaxDbP09327.
PRIDEP09327.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000248444; ENSP00000248444; ENSG00000127831.
ENST00000440053; ENSP00000409270; ENSG00000127831.
GeneID7429.
KEGGhsa:7429.
UCSCuc002via.3. human. [P09327-1]

Organism-specific databases

CTD7429.
GeneCardsGC02P219285.
HGNCHGNC:12690. VIL1.
HPACAB002452.
HPA006884.
HPA006885.
MIM193040. gene.
neXtProtNX_P09327.
PharmGKBPA37309.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG304849.
HOGENOMHOG000233630.
HOVERGENHBG004183.
InParanoidP09327.
KOK05761.
OMAVPVESKW.
OrthoDBEOG7288RJ.
PhylomeDBP09327.
TreeFamTF313468.

Gene expression databases

ArrayExpressP09327.
BgeeP09327.
CleanExHS_VIL1.
GenevestigatorP09327.

Family and domain databases

Gene3D1.10.950.10. 1 hit.
3.40.20.10. 6 hits.
InterProIPR029006. ADF-H/Gelsolin-like_dom.
IPR007123. Gelsolin-like_dom.
IPR007122. Villin/Gelsolin.
IPR003128. Villin_headpiece.
[Graphical view]
PANTHERPTHR11977. PTHR11977. 1 hit.
PfamPF00626. Gelsolin. 6 hits.
PF02209. VHP. 1 hit.
[Graphical view]
PRINTSPR00597. GELSOLIN.
SMARTSM00262. GEL. 6 hits.
SM00153. VHP. 1 hit.
[Graphical view]
SUPFAMSSF47050. SSF47050. 1 hit.
PROSITEPS51089. HP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP09327.
GenomeRNAi7429.
NextBio29096.
PROP09327.
SOURCESearch...

Entry information

Entry nameVILI_HUMAN
AccessionPrimary (citable) accession number: P09327
Secondary accession number(s): B2R9A7, Q53S11, Q96AC8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: March 3, 2009
Last modified: July 9, 2014
This is version 146 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM