VILI_MOUSE
ID VILI_MOUSE Reviewed; 827 AA.
AC Q62468; Q149B6; Q91WH4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Villin-1;
GN Name=Vil1; Synonyms=Vil;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1601186; DOI=10.1016/0012-1606(92)90195-m;
RA Ezzell R.M., Leung J., Collins K., Chafel M.M., Cardozo T.J.,
RA Matsudaira P.T.;
RT "Expression and localization of villin, fimbrin, and myosin I in
RT differentiating mouse F9 teratocarcinoma cells.";
RL Dev. Biol. 151:575-585(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Brain, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10459016; DOI=10.1083/jcb.146.4.819;
RA Ferrary E., Cohen-Tannoudji M., Pehau-Arnaudet G., Lapillonne A.,
RA Athman R., Ruiz T., Boulouha L., El Marjou F., Doye A., Fontaine J.J.,
RA Antony C., Babinet C., Louvard D., Jaisser F., Robine S.;
RT "In vivo, villin is required for Ca(2+)-dependent F-actin disruption in
RT intestinal brush borders.";
RL J. Cell Biol. 146:819-830(1999).
RN [4]
RP FUNCTION, TYROSINE PHOSPHORYLATION, DISRUPTION PHENOTYPE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12937273; DOI=10.1091/mbc.e03-02-0091;
RA Athman R., Louvard D., Robine S.;
RT "Villin enhances hepatocyte growth factor-induced actin cytoskeleton
RT remodeling in epithelial cells.";
RL Mol. Biol. Cell 14:4641-4653(2003).
RN [5]
RP FUNCTION IN SHIGELLA FLEXNERI INFECTION, DISRUPTION PHENOTYPE, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16008578; DOI=10.1111/j.1462-5822.2005.00535.x;
RA Athman R., Fernandez M.I., Gounon P., Sansonetti P., Louvard D.,
RA Philpott D., Robine S.;
RT "Shigella flexneri infection is dependent on villin in the mouse intestine
RT and in primary cultures of intestinal epithelial cells.";
RL Cell. Microbiol. 7:1109-1116(2005).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18198174; DOI=10.1074/jbc.m707962200;
RA Wang Y., Srinivasan K., Siddiqui M.R., George S.P., Tomar A., Khurana S.;
RT "A novel role for villin in intestinal epithelial cell survival and
RT homeostasis.";
RL J. Biol. Chem. 283:9454-9464(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-735 AND SER-776, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Epithelial cell-specific Ca(2+)-regulated actin-modifying
CC protein that modulates the reorganization of microvillar actin
CC filaments. Plays a role in the actin nucleation, actin filament bundle
CC assembly, actin filament capping and severing. Binds
CC phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid
CC (LPA); binds LPA with higher affinity than PIP2. Binding to LPA
CC increases its phosphorylation by SRC and inhibits all actin-modifying
CC activities. Binding to PIP2 inhibits actin-capping and -severing
CC activities but enhances actin-bundling activity. Regulates the
CC intestinal epithelial cell morphology, cell invasion, cell migration
CC and apoptosis. Protects against apoptosis induced by dextran sodium
CC sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate
CC cell death by maintaining mitochondrial integrity. Enhances hepatocyte
CC growth factor (HGF)-induced epithelial cell motility, chemotaxis and
CC wound repair. Upon S.flexneri cell infection, its actin-severing
CC activity enhances actin-based motility of the bacteria and plays a role
CC during the dissemination. {ECO:0000269|PubMed:12937273,
CC ECO:0000269|PubMed:16008578, ECO:0000269|PubMed:18198174}.
CC -!- SUBUNIT: Monomer. Homodimer; homodimerization is necessary for actin-
CC bundling. Associates with F-actin; phosphorylation at tyrosine residues
CC decreases the association with F-actin. Interacts (phosphorylated at C-
CC terminus tyrosine phosphorylation sites) with PLCG1 (via the SH2
CC domains) (By similarity). Interacts (phosphorylated form) with PLCG1;
CC the interaction is enhanced by hepatocyte growth factor (HGF).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000250}. Cell
CC projection, microvillus {ECO:0000250}. Cell projection, lamellipodium.
CC Cell projection, ruffle {ECO:0000250}. Cell projection, filopodium tip.
CC Cell projection, filopodium. Note=Rapidly redistributed to ruffles and
CC lamellipodia structures in response to autotaxin, lysophosphatidic acid
CC (LPA) and epidermal growth factor (EGF) treatment (By similarity).
CC Relocalized in the tip of cellular protrusions and filipodial
CC extensions upon infection with S.flexneri in primary intestinal
CC epithelial cells (IEC) and in the tail-like structures forming the
CC actin comets of S.flexneri. Redistributed to the leading edge of
CC hepatocyte growth factor (HGF)-induced lamellipodia. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in small intestin, colon, kidney and
CC enterocytes (at protein level). {ECO:0000269|PubMed:10459016,
CC ECO:0000269|PubMed:16008578}.
CC -!- DOMAIN: Consists of a large core fragment in the N-terminal portion and
CC a small headpiece (HP) in the C-terminal portion. The core fragment is
CC necessary for both actin-nucleating and -severing activities, whereas
CC the HP binds F-actin strongly in both the presence and absence of
CC calcium and is necessary in actin-bundling activity. The Gelsolin-like
CC 1 repeat is necessary for the actin-capping activity. The entire core
CC fragment is necessary for the actin-severing activity. Two major
CC calcium-sensitive sites are involved in conformational changes and
CC determine separate functional properties: the first site (Glu-25, Asp-
CC 44 and Glu-74) regulates the actin-capping and actin-severing
CC activities; while the second site (Asp-61, Asp-86 and Ala-93) regulates
CC only the actin-severing activity (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine residues by SRC. The unphosphorylated
CC form increases the initial rate of actin-nucleating activity, whereas
CC the tyrosine phosphorylated form inhibits actin-nucleating activity,
CC enhances actin-bundling activity and enhances actin-severing activity
CC by reducing high Ca(2+) requirements. The tyrosine phosphorylated form
CC does not regulate actin-capping activity. Tyrosine phosphorylation is
CC essential for cell migration: tyrosine phosphorylation sites in the N-
CC terminus half regulate actin reorganization and cell morphology,
CC whereas tyrosine phosphorylation sites in the C-terminus half regulate
CC cell migration via interaction with PLCG1 (By similarity). Tyrosine
CC phosphorylation is induced by epidermal growth factor (EGF) and
CC stimulates cell migration. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile. The ultrastructure
CC of the intestinal brush border is normal. Show increase epithelial cell
CC apoptosis and are more sensitive to extran sodium sulfate-induced
CC colitis. Newborn mice inoculated with S.flexneri are not susceptible to
CC infection; cell invasion and intestinal inflammation were not observed,
CC even though bacteria were seen in large number in the intestinal lumen,
CC close to the intestinal epithelial cells (IEC) brush border.
CC {ECO:0000269|PubMed:10459016, ECO:0000269|PubMed:12937273,
CC ECO:0000269|PubMed:16008578, ECO:0000269|PubMed:18198174}.
CC -!- SIMILARITY: Belongs to the villin/gelsolin family. {ECO:0000305}.
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DR EMBL; M98454; AAA40554.1; -; mRNA.
DR EMBL; BC117875; AAI17876.1; -; mRNA.
DR EMBL; BC145671; AAI45672.1; -; mRNA.
DR EMBL; BC015267; AAH15267.1; -; mRNA.
DR CCDS; CCDS15049.1; -.
DR RefSeq; NP_033535.2; NM_009509.2.
DR AlphaFoldDB; Q62468; -.
DR SMR; Q62468; -.
DR BioGRID; 204521; 3.
DR IntAct; Q62468; 5.
DR STRING; 10090.ENSMUSP00000027366; -.
DR iPTMnet; Q62468; -.
DR PhosphoSitePlus; Q62468; -.
DR jPOST; Q62468; -.
DR MaxQB; Q62468; -.
DR PaxDb; Q62468; -.
DR PeptideAtlas; Q62468; -.
DR PRIDE; Q62468; -.
DR ProteomicsDB; 297912; -.
DR Antibodypedia; 1531; 702 antibodies from 41 providers.
DR DNASU; 22349; -.
DR Ensembl; ENSMUST00000027366; ENSMUSP00000027366; ENSMUSG00000026175.
DR GeneID; 22349; -.
DR KEGG; mmu:22349; -.
DR UCSC; uc007bmb.2; mouse.
DR CTD; 7429; -.
DR MGI; MGI:98930; Vil1.
DR VEuPathDB; HostDB:ENSMUSG00000026175; -.
DR eggNOG; KOG0443; Eukaryota.
DR GeneTree; ENSGT00940000160544; -.
DR HOGENOM; CLU_002568_3_1_1; -.
DR InParanoid; Q62468; -.
DR OMA; FNWDYSK; -.
DR OrthoDB; 1376537at2759; -.
DR PhylomeDB; Q62468; -.
DR TreeFam; TF313468; -.
DR BioGRID-ORCS; 22349; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Vil1; mouse.
DR PRO; PR:Q62468; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q62468; protein.
DR Bgee; ENSMUSG00000026175; Expressed in small intestine Peyer's patch and 88 other tissues.
DR ExpressionAtlas; Q62468; baseline and differential.
DR Genevisible; Q62468; MM.
DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0032432; C:actin filament bundle; ISS:UniProtKB.
DR GO; GO:0005903; C:brush border; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0032433; C:filopodium tip; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0035727; F:lysophosphatidic acid binding; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0051693; P:actin filament capping; ISS:UniProtKB.
DR GO; GO:0030042; P:actin filament depolymerization; ISS:UniProtKB.
DR GO; GO:0030041; P:actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0051014; P:actin filament severing; ISO:MGI.
DR GO; GO:0045010; P:actin nucleation; IEA:InterPro.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IBA:GO_Central.
DR GO; GO:0051016; P:barbed-end actin filament capping; ISO:MGI.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0060327; P:cytoplasmic actin-based contraction involved in cell motility; ISO:MGI.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0001951; P:intestinal D-glucose absorption; IGI:UniProtKB.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; ISS:UniProtKB.
DR GO; GO:0030836; P:positive regulation of actin filament depolymerization; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISS:UniProtKB.
DR GO; GO:2000394; P:positive regulation of lamellipodium morphogenesis; ISO:MGI.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IGI:UniProtKB.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IGI:UniProtKB.
DR GO; GO:0051125; P:regulation of actin nucleation; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:2000392; P:regulation of lamellipodium morphogenesis; IDA:UniProtKB.
DR GO; GO:0032532; P:regulation of microvillus length; IGI:UniProtKB.
DR GO; GO:0061041; P:regulation of wound healing; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; ISO:MGI.
DR GO; GO:1902896; P:terminal web assembly; IGI:UniProtKB.
DR Gene3D; 1.10.950.10; -; 1.
DR Gene3D; 3.40.20.10; -; 6.
DR InterPro; IPR029006; ADF-H/Gelsolin-like_dom_sf.
DR InterPro; IPR007123; Gelsolin-like_dom.
DR InterPro; IPR036180; Gelsolin-like_dom_sf.
DR InterPro; IPR030007; Villin-1.
DR InterPro; IPR007122; Villin/Gelsolin.
DR InterPro; IPR003128; Villin_headpiece.
DR InterPro; IPR036886; Villin_headpiece_dom_sf.
DR PANTHER; PTHR11977; PTHR11977; 1.
DR PANTHER; PTHR11977:SF35; PTHR11977:SF35; 1.
DR Pfam; PF00626; Gelsolin; 6.
DR Pfam; PF02209; VHP; 1.
DR PRINTS; PR00597; GELSOLIN.
DR SMART; SM00262; GEL; 6.
DR SMART; SM00153; VHP; 1.
DR SUPFAM; SSF47050; SSF47050; 1.
DR SUPFAM; SSF82754; SSF82754; 2.
DR PROSITE; PS51089; HP; 1.
PE 1: Evidence at protein level;
KW Actin capping; Actin-binding; Apoptosis; Calcium; Cell projection;
KW Cytoplasm; Cytoskeleton; Metal-binding; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..827
FT /note="Villin-1"
FT /id="PRO_0000218728"
FT REPEAT 27..76
FT /note="Gelsolin-like 1"
FT REPEAT 148..188
FT /note="Gelsolin-like 2"
FT REPEAT 265..309
FT /note="Gelsolin-like 3"
FT REPEAT 407..457
FT /note="Gelsolin-like 4"
FT REPEAT 528..568
FT /note="Gelsolin-like 5"
FT REPEAT 631..672
FT /note="Gelsolin-like 6"
FT DOMAIN 761..827
FT /note="HP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00595"
FT REGION 1..734
FT /note="Core"
FT REGION 1..126
FT /note="Necessary for homodimerization"
FT /evidence="ECO:0000250"
FT REGION 112..119
FT /note="LPA/PIP2-binding site 1"
FT /evidence="ECO:0000250"
FT REGION 138..146
FT /note="LPA/PIP2-binding site 2"
FT /evidence="ECO:0000250"
FT REGION 735..827
FT /note="Headpiece"
FT REGION 816..824
FT /note="LPA/PIP2-binding site 3"
FT /evidence="ECO:0000250"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09327"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 776
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 192
FT /note="A -> P (in Ref. 1; AAA40554)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 827 AA; 92775 MW; 15601DFBA04B500E CRC64;
MTKLNAQVKG SLNITTPGIQ IWRIEAMQMV PVPSSTFGSF FDGDCYVVLA IHKTSSTLSY
DIHYWIGQDS SQDEQGAAAI YTTQMDDYLK GRAVQHREVQ GNESETFRSY FKQGLVIRKG
GVASGMKHVE TNSCDVQRLL HVKGKRNVLA GEVEMSWKSF NRGDVFLLDL GKLIIQWNGP
ESNRMERLRG MALAKEIRDQ ERGGRTYVGV VDGEKEGDSP QLMAIMNHVL GPRKELKAAI
SDSVVEPAAK AALKLYHVSD SEGKLVVREV ATRPLTQDLL KHEDCYILDQ GGLKIFVWKG
KNANAQERSG AMSQALNFIK AKQYPPSTQV EVQNDGAESP IFQQLFQKWT VPNRTSGLGK
THTVGSVAKV EQVKFDALTM HVQPQVAAQQ KMVDDGSGEV QVWRIEDLEL VPVESKWLGH
FYGGDCYLLL YTYLIGEKQH YLLYIWQGSQ ASQDEIAASA YQAVLLDQKY NDEPVQIRVT
MGKEPPHLMS IFKGRMVVYQ GGTSRKNNLE PVPSTRLFQV RGTNADNTKA FEVTARATSL
NSNDVFILKT PSCCYLWCGK GCSGDEREMA KMVADTISRT EKQVVVEGQE PANFWMALGG
KAPYANTKRL QEENQVITPR LFECSNQTGR FLATEIFDFN QDDLEEEDVF LLDVWDQVFF
WIGKHANEEE KKAAATTVQE YLKTHPGNRD LETPIIVVKQ GHEPPTFTGW FLAWDPFKWS
NTKSYDDLKA ELGNSGDWSQ IADEVMSPKV DVFTANTSLS SGPLPTFPLE QLVNKSVEDL
PEGVDPSRKE EHLSTEDFTR ALGMTPAAFS ALPRWKQQNI KKEKGLF
