VILI_BOVIN
ID VILI_BOVIN Reviewed; 827 AA.
AC Q3SZP7;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 25-MAY-2022, entry version 86.
DE RecName: Full=Villin-1;
GN Name=VIL1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
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). Interacts (phosphorylated form) with PLCG1; the interaction
CC is enhanced by hepatocyte growth factor (HGF) (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000250}. Cell
CC projection, lamellipodium {ECO:0000250}. Cell projection, ruffle
CC {ECO:0000250}. Cell projection, microvillus {ECO:0000250}. Cell
CC projection, filopodium tip {ECO:0000250}. Cell projection, filopodium
CC {ECO:0000250}. Note=Rapidly redistributed to ruffles and lamellipodia
CC structures in response to autotaxin, lysophosphatidic acid (LPA) and
CC epidermal growth factor (EGF) treatment. Redistributed to the leading
CC edge of hepatocyte growth factor (HGF)-induced lamellipodia (By
CC similarity). {ECO:0000250}.
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. Tyrosine phosphorylation is
CC induced by epidermal growth factor (EGF) and stimulates cell migration
CC (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the villin/gelsolin family. {ECO:0000305}.
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DR EMBL; BC102759; AAI02760.1; -; mRNA.
DR AlphaFoldDB; Q3SZP7; -.
DR SMR; Q3SZP7; -.
DR STRING; 9913.ENSBTAP00000024683; -.
DR PaxDb; Q3SZP7; -.
DR PeptideAtlas; Q3SZP7; -.
DR PRIDE; Q3SZP7; -.
DR eggNOG; KOG0443; Eukaryota.
DR InParanoid; Q3SZP7; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0032432; C:actin filament bundle; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0032433; C:filopodium tip; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
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; ISS:UniProtKB.
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; ISS:UniProtKB.
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; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0060327; P:cytoplasmic actin-based contraction involved in cell motility; ISS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; ISS:UniProtKB.
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: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; ISS:UniProtKB.
DR GO; GO:0061041; P:regulation of wound healing; ISS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; ISS: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 2: Evidence at transcript level;
KW Actin capping; Actin-binding; Apoptosis; Calcium; Cell projection;
KW Cytoplasm; Cytoskeleton; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..827
FT /note="Villin-1"
FT /id="PRO_0000271393"
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:0000250|UniProtKB:Q62468"
SQ SEQUENCE 827 AA; 92802 MW; F760711EB6334755 CRC64;
MTKLSAQVKG SLNITTPGVQ IWRIEAMQMV PVPSNSFGSF FDGDCYVIQA IHKTGSNLSY
DIHYWIGQAS SQDEQGAAAI YTTQMDDFLK GRAVQHREVQ GNESDTFRGY FKKGIVIRKG
GVASGMKQVE TNSYDIQRLL HVKGKRNVVA GEVEMSWKSF NRGDVFLLDL GKLIIQWNGP
ESNHMERLRG MNLAKEIRDQ ERGGRTYVGV VDGEDEKASP QLMEIMNHVL GQRKELKAAV
ADTVVEPALK AALKLYHVSD SEGKVVVREI ATQPLTQDLL SHEDCYILDQ GGLKIYVWKG
KNANAQEKKE AMNQALNFIK AKQYPPSTQV ELQNDGAESA VFQQLFQKWT VPNRTTGLGK
THTVGSVAKV EQVKFDAMSM HVQPQVAAQQ KMVDDGSGEV QMWRIENLEL VPVNTKWLGH
FFGGDCYLLL YTYFINEKPH YLLYIWQGSQ ASQDEITASA YQAVILDQEY NNEPVQIRVP
MGKEPPHLMS IFKGCMVVYQ GGTSRANSVE PVPSTRLFQV RGTSANNTKA FEVSPRAASL
NSNDVFILKT QSCCYLWCGK GCSGDEREMA KMVADTVSRT EKQVVVEGQE PANFWLALGG
KAPYASTKRL QEENLVITPR LFECSNQTGR FLATEIPDFN QDDLEEDDVF LLDVWDQVFF
WIGKNANEDE KKAAATTVQE YLKTHPGGRD LETPIIVVKQ GHEPPTFTGW FLAWDPFKWN
NSKSYEDLKA ELGNSGDWSQ ITAELTSSKP EAFNANSNLS SGPLPIFPLE QLVNKPTEEL
PEGVDPSRRE EHLSIEDFTR ALGMTPSAFW ALPRWKQQNL KKEKGLF
