VILI_PIG
ID VILI_PIG Reviewed; 827 AA.
AC Q29261;
DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 2.
DT 25-MAY-2022, entry version 92.
DE RecName: Full=Villin-1;
GN Name=VIL1; Synonyms=VIL;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Intestine;
RX PubMed=14681463; DOI=10.1093/nar/gkh037;
RA Uenishi H., Eguchi T., Suzuki K., Sawazaki T., Toki D., Shinkai H.,
RA Okumura N., Hamasima N., Awata T.;
RT "PEDE (Pig EST Data Explorer): construction of a database for ESTs derived
RT from porcine full-length cDNA libraries.";
RL Nucleic Acids Res. 32:D484-D488(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 73-203.
RC TISSUE=Small intestine;
RX PubMed=8672129; DOI=10.1007/s003359900153;
RA Winteroe A.K., Fredholm M., Davies W.;
RT "Evaluation and characterization of a porcine small intestine cDNA library:
RT analysis of 839 clones.";
RL Mamm. Genome 7:509-517(1996).
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. Tyrosine phosphorylation is induced by epidermal growth
CC factor (EGF) and stimulates cell migration (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the villin/gelsolin family. {ECO:0000305}.
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DR EMBL; AK231370; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; F14554; CAA23122.1; -; mRNA.
DR AlphaFoldDB; Q29261; -.
DR SMR; Q29261; -.
DR STRING; 9823.ENSSSCP00000017159; -.
DR PaxDb; Q29261; -.
DR PeptideAtlas; Q29261; -.
DR PRIDE; Q29261; -.
DR eggNOG; KOG0443; Eukaryota.
DR InParanoid; Q29261; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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_0000218729"
FT REPEAT 28..107
FT /note="Gelsolin-like 1"
FT REPEAT 148..216
FT /note="Gelsolin-like 2"
FT REPEAT 269..342
FT /note="Gelsolin-like 3"
FT REPEAT 409..489
FT /note="Gelsolin-like 4"
FT REPEAT 528..595
FT /note="Gelsolin-like 5"
FT REPEAT 634..707
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 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"
FT CONFLICT 186
FT /note="E -> V (in Ref. 2; CAA23122)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="R -> P (in Ref. 2; CAA23122)"
FT /evidence="ECO:0000305"
FT CONFLICT 201..202
FT /note="ER -> GA (in Ref. 2; CAA23122)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 827 AA; 92701 MW; B48E433074120A26 CRC64;
MTKLNAQVKG SLNVTTPGVQ IWRIEAMQMV PVSSSTYGSF FDGDCYIVLA IHKTGSNLSY
DIHYWIGQDS SQDEQGAAAI YTTLMDDFLK GRAVQHREVQ GNESEAFRGY FKQGIVIRKG
GVASGMKKVE TNSYDIQRLL HVKGKRNVVA GEVEMSWKSF NRGDVFLLDL GKLIIQWNGP
ESNRMERLRG MTLAKEIRDQ ERGGRTYVGV VDGEDEKASP QLMEIMNYVL GQRKELKAAV
PDTVVEPALK AALKLYHVSD SEGKVVVREV ATRPLTQDLL SHEDCYILDQ GGLKIYVWKG
KNANPQEKKE AMNQALNFIK AKQYPPSTQV EVQNDGAESA VFQQLFQKWT VPNQTSGLGK
THTVGSVAKV EQVKFDATSM HVQPQVAAQQ KMVDDGSGEV EIWRIENLDL VPVESKWVGH
FYGGDCYLLL YTYLIGEKQH YLLYIWQGSQ ASQDEITASA YQAVILDQKY NNEPVQIRVP
MGKEPPHLMS IFKGRMVVYQ GGTSRANSTE PVPSTRLFQV RGTSVNNTKA FEVPARATSL
NSNDIFVLKT QSCCYLWCGK GCSGDEREMA KMVADTISRT EKQVVVEGQE PANFWVALGG
KAPYASSKRL QEETLVITPR LFECSNQTGR FLATEIPDFN QDDLEEDDVF LLDVWDQVFF
WIGKNANEDE KKAAAVTAQE YLKTHPSGRD PETPIIVVKQ GYEPPTFTGW FLAWDPFKWS
DSKSYEDLKA ELGNSGDWSQ ITAEIKNPKP DVFNANTNLS SGPLPIFPLE QLVNKPAEEL
PQGVDPSRRE EHLSIEDFTK ALGMTPAAFS ALPRWKQQNL KKEKGLF
