VILI_HUMAN
ID VILI_HUMAN Reviewed; 827 AA.
AC P09327; B2R9A7; Q53S11; Q96AC8;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 4.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Villin-1;
GN Name=VIL1; Synonyms=VIL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 2-13.
RC TISSUE=Intestine;
RX PubMed=2846586; DOI=10.1083/jcb.107.5.1759;
RA Arpin M., Pringault E., Finidori J., Garcia A., Jeltsch J.-M., Louvard D.,
RA van de Kerckhove B.;
RT "Sequence of human villin: a large duplicated domain homologous with other
RT actin-severing proteins and a unique small carboxy-terminal domain related
RT to villin specificity.";
RL J. Cell Biol. 107:1759-1766(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 718-827 (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=3453110; DOI=10.1002/j.1460-2075.1986.tb04618.x;
RA Pringault E., Arpin M., Garcia A., Finidori J., Louvard D.;
RT "A human villin cDNA clone to investigate the differentiation of intestinal
RT and kidney cells in vivo and in culture.";
RL EMBO J. 5:3119-3124(1986).
RN [7]
RP FUNCTION.
RX PubMed=3087992; DOI=10.1016/s0021-9258(18)67650-1;
RA Northrop J., Weber A., Mooseker M.S., Franzini-Armstrong C., Bishop M.F.,
RA Dubyak G.R., Tucker M., Walsh T.P.;
RT "Different calcium dependence of the capping and cutting activities of
RT villin.";
RL J. Biol. Chem. 261:9274-9281(1986).
RN [8]
RP FUNCTION, ASSOCIATION WITH F-ACTIN, AND PHOSPHORYLATION.
RX PubMed=11500485; DOI=10.1074/jbc.c100418200;
RA Zhai L., Zhao P., Panebra A., Guerrerio A.L., Khurana S.;
RT "Tyrosine phosphorylation of villin regulates the organization of the actin
RT cytoskeleton.";
RL J. Biol. Chem. 276:36163-36167(2001).
RN [9]
RP PHOSPHORYLATION BY SRC, PHOSPHORYLATION AT TYROSINE RESIDUES, AND
RP MUTAGENESIS OF TYR-46; TYR-60; TYR-81 AND TYR-256.
RX PubMed=12269817; DOI=10.1021/bi0263762;
RA Zhai L., Kumar N., Panebra A., Zhao P., Parrill A.L., Khurana S.;
RT "Regulation of actin dynamics by tyrosine phosphorylation: identification
RT of tyrosine phosphorylation sites within the actin-severing domain of
RT villin.";
RL Biochemistry 41:11750-11760(2002).
RN [10]
RP POSSIBLE INVOLVEMENT IN BILIARY ATRESIA, AND TISSUE SPECIFICITY.
RX PubMed=14550699; DOI=10.1016/s0140-6736(03)14467-4;
RA Phillips M.J., Azuma T., Meredith S.L., Squire J.A., Ackerley C.A.,
RA Pluthero F.G., Roberts E.A., Superina R.A., Levy G.A., Marsden P.A.;
RT "Abnormalities in villin gene expression and canalicular microvillus
RT structure in progressive cholestatic liver disease of childhood.";
RL Lancet 362:1112-1119(2003).
RN [11]
RP FUNCTION, INTERACTION WITH PHOSPHATIDYLINOSITOL, AND MUTAGENESIS OF
RP ARG-138; LYS-145; ARG-146; LYS-822 AND LYS-824.
RX PubMed=14594952; DOI=10.1074/jbc.m308878200;
RA Kumar N., Zhao P., Tomar A., Galea C.A., Khurana S.;
RT "Association of villin with phosphatidylinositol 4,5-bisphosphate regulates
RT the actin cytoskeleton.";
RL J. Biol. Chem. 279:3096-3110(2004).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF ASP-467 AND ASP-715.
RX PubMed=15084600; DOI=10.1074/jbc.c400110200;
RA Kumar N., Khurana S.;
RT "Identification of a functional switch for actin severing by cytoskeletal
RT proteins.";
RL J. Biol. Chem. 279:24915-24918(2004).
RN [13]
RP FUNCTION, CALCIUM-BINDING, AND MUTAGENESIS OF GLU-25; ASP-44; ASP-61;
RP GLU-74; ASP-86 AND ALA-93.
RX PubMed=15272027; DOI=10.1074/jbc.m405424200;
RA Kumar N., Tomar A., Parrill A.L., Khurana S.;
RT "Functional dissection and molecular characterization of calcium-sensitive
RT actin-capping and actin-depolymerizing sites in villin.";
RL J. Biol. Chem. 279:45036-45046(2004).
RN [14]
RP FUNCTION, MUTAGENESIS OF TYR-46; TYR-60; TYR-81 AND TYR-256, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15342783; DOI=10.1091/mbc.e04-05-0431;
RA Tomar A., Wang Y., Kumar N., George S., Ceacareanu B., Hassid A.,
RA Chapman K.E., Aryal A.M., Waters C.M., Khurana S.;
RT "Regulation of cell motility by tyrosine phosphorylated villin.";
RL Mol. Biol. Cell 15:4807-4817(2004).
RN [15]
RP FUNCTION, INTERACTION WITH PLCG1, PHOSPHORYLATION AT TYROSINE RESIDUES,
RP MUTAGENESIS OF TYR-46; TYR-60; TYR-81; TYR-256; TYR-286; TYR-324; TYR-461;
RP TYR-555; TYR-604 AND TYR-725, AND SUBCELLULAR LOCATION.
RX PubMed=16921170; DOI=10.1074/jbc.m604323200;
RA Tomar A., George S., Kansal P., Wang Y., Khurana S.;
RT "Interaction of phospholipase C-gamma1 with villin regulates epithelial
RT cell migration.";
RL J. Biol. Chem. 281:31972-31986(2006).
RN [16]
RP FUNCTION, INTERACTION WITH PLCG1, PHOSPHORYLATION AT TYROSINE RESIDUES,
RP MUTAGENESIS OF TYR-46; TYR-60; TYR-81; TYR-256; TYR-286; TYR-324; TYR-461;
RP TYR-555; TYR-604 AND TYR-725, AND SUBCELLULAR LOCATION.
RX PubMed=17229814; DOI=10.1152/ajpcell.00420.2006;
RA Wang Y., Tomar A., George S.P., Khurana S.;
RT "Obligatory role for phospholipase C-gamma(1) in villin-induced epithelial
RT cell migration.";
RL Am. J. Physiol. 292:C1775-C1786(2007).
RN [17]
RP FUNCTION, HOMODIMERIZATION, AND SUBCELLULAR LOCATION.
RX PubMed=17606613; DOI=10.1074/jbc.m703617200;
RA George S.P., Wang Y., Mathew S., Srinivasan K., Khurana S.;
RT "Dimerization and actin-bundling properties of villin and its role in the
RT assembly of epithelial cell brush borders.";
RL J. Biol. Chem. 282:26528-26541(2007).
RN [18]
RP FUNCTION, MUTAGENESIS OF ASP-61; GLU-74; 86-ASP--GLY-91 AND
RP 125-GLY--VAL-129, AND SUBCELLULAR LOCATION.
RX PubMed=17182858; DOI=10.1091/mbc.e06-05-0423;
RA Revenu C., Courtois M., Michelot A., Sykes C., Louvard D., Robine S.;
RT "Villin severing activity enhances actin-based motility in vivo.";
RL Mol. Biol. Cell 18:827-838(2007).
RN [19]
RP FUNCTION, MUTAGENESIS OF TYR-46; TYR-60; TYR-81; TYR-256; TYR-286; TYR-324;
RP TYR-461; TYR-555; TYR-604 AND TYR-725, AND SUBCELLULAR LOCATION.
RX PubMed=18054784; DOI=10.1016/j.yexcr.2007.10.028;
RA Khurana S., Tomar A., George S.P., Wang Y., Siddiqui M.R., Guo H.,
RA Tigyi G., Mathew S.;
RT "Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by
RT redistribution of the actin modifying protein villin to the developing
RT lamellipodia.";
RL Exp. Cell Res. 314:530-542(2008).
RN [20]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [21]
RP FUNCTION, INTERACTION WITH LYSOPHOSPHATIDIC ACID, ASSOCIATION WITH F-ACTIN,
RP AND SUBCELLULAR LOCATION.
RX PubMed=19808673; DOI=10.1074/jbc.c109.060830;
RA Tomar A., George S.P., Mathew S., Khurana S.;
RT "Differential effects of lysophosphatidic acid and phosphatidylinositol
RT 4,5-bisphosphate on actin dynamics by direct association with the actin-
RT binding protein villin.";
RL J. Biol. Chem. 284:35278-35282(2009).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-366, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP STRUCTURE BY NMR OF 793-827, ASSOCIATION WITH F-ACTIN, AND MUTAGENESIS OF
RP TRP-815.
RX PubMed=15096633; DOI=10.1110/ps.03518104;
RA Vermeulen W., Vanhaesebrouck P., Van Troys M., Verschueren M., Fant F.,
RA Goethals M., Ampe C., Martins J.C., Borremans F.A.;
RT "Solution structures of the C-terminal headpiece subdomains of human villin
RT and advillin, evaluation of headpiece F-actin-binding requirements.";
RL Protein Sci. 13:1276-1287(2004).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 360-720.
RX PubMed=19491107; DOI=10.1074/jbc.m109.019760;
RA Wang H., Chumnarnsilpa S., Loonchanta A., Li Q., Kuan Y.M., Robine S.,
RA Larsson M., Mihalek I., Burtnick L.D., Robinson R.C.;
RT "Helix straightening as an activation mechanism in the gelsolin superfamily
RT of actin regulatory proteins.";
RL J. Biol. Chem. 284:21265-21269(2009).
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:11500485,
CC ECO:0000269|PubMed:14594952, ECO:0000269|PubMed:15084600,
CC ECO:0000269|PubMed:15272027, ECO:0000269|PubMed:15342783,
CC ECO:0000269|PubMed:16921170, ECO:0000269|PubMed:17182858,
CC ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:17606613,
CC ECO:0000269|PubMed:18054784, ECO:0000269|PubMed:18198174,
CC ECO:0000269|PubMed:19808673, ECO:0000269|PubMed:3087992}.
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 -!- INTERACTION:
CC P09327; P19174: PLCG1; NbExp=5; IntAct=EBI-746958, EBI-79387;
CC P09327; P09327: VIL1; NbExp=9; IntAct=EBI-746958, EBI-746958;
CC P09327-2; P42858: HTT; NbExp=3; IntAct=EBI-25958818, EBI-466029;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell projection,
CC lamellipodium. Cell projection, ruffle. Cell projection, microvillus.
CC Cell projection, filopodium tip {ECO:0000250}. Cell projection,
CC filopodium {ECO:0000250}. Note=Relocalized in the tip of cellular
CC protrusions and filipodial extensions upon infection with S.flexneri in
CC primary intestinal epithelial cells (IEC) and in the tail-like
CC structures forming the actin comets of S.flexneri. Redistributed to the
CC leading edge of hepatocyte growth factor (HGF)-induced lamellipodia (By
CC similarity). Rapidly redistributed to ruffles and lamellipodia
CC structures in response to autotaxin, lysophosphatidic acid (LPA) and
CC epidermal growth factor (EGF) treatment. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P09327-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P09327-2; Sequence=VSP_054436, VSP_054437;
CC -!- TISSUE SPECIFICITY: Specifically expressed in epithelial cells. Major
CC component of microvilli of intestinal epithelial cells and kidney
CC proximal tubule cells. Expressed in canalicular microvilli of
CC hepatocytes (at protein level). {ECO:0000269|PubMed:14550699,
CC ECO:0000269|PubMed:3453110}.
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.
CC -!- PTM: Tyrosine phosphorylation is induced by epidermal growth factor
CC (EGF) and stimulates cell migration (By similarity). Phosphorylated on
CC tyrosine residues by SRC. The unphosphorylated form increases the
CC initial rate of actin-nucleating activity, whereas the tyrosine-
CC phosphorylated form inhibits actin-nucleating activity, enhances actin-
CC bundling activity and enhances actin-severing activity by reducing high
CC Ca(2+) requirements. The tyrosine-phosphorylated form does not regulate
CC actin-capping activity. Tyrosine phosphorylation is essential for cell
CC migration: tyrosine phosphorylation sites in the N-terminus half
CC regulate actin reorganization and cell morphology, whereas tyrosine
CC phosphorylation sites in the C-terminus half regulate cell migration
CC via interaction with PLCG1. {ECO:0000250, ECO:0000269|PubMed:11500485,
CC ECO:0000269|PubMed:12269817, ECO:0000269|PubMed:16921170,
CC ECO:0000269|PubMed:17229814}.
CC -!- DISEASE: Note=Biliary atresia is a chronic and progressive cholestatic
CC liver disease of chilhood characterized by an abnormal villin gene
CC expression and severe malformation of canalicular microvillus
CC structure.
CC -!- SIMILARITY: Belongs to the villin/gelsolin family. {ECO:0000305}.
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DR EMBL; X12901; CAA31386.1; -; mRNA.
DR EMBL; AK313709; BAG36454.1; -; mRNA.
DR EMBL; AC021016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073838; AAY14886.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70619.1; -; Genomic_DNA.
DR EMBL; BC017303; AAH17303.1; -; mRNA.
DR EMBL; X04657; CAA28355.1; -; mRNA.
DR CCDS; CCDS2417.1; -. [P09327-1]
DR PIR; A31642; A31642.
DR RefSeq; NP_009058.2; NM_007127.2. [P09327-1]
DR PDB; 1UNC; NMR; -; A=793-827.
DR PDB; 3FG7; X-ray; 2.00 A; A/B=360-720.
DR PDBsum; 1UNC; -.
DR PDBsum; 3FG7; -.
DR AlphaFoldDB; P09327; -.
DR BMRB; P09327; -.
DR SMR; P09327; -.
DR BioGRID; 113270; 15.
DR IntAct; P09327; 6.
DR MINT; P09327; -.
DR STRING; 9606.ENSP00000248444; -.
DR GlyConnect; 1893; 6 N-Linked glycans (1 site).
DR GlyGen; P09327; 2 sites, 6 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P09327; -.
DR PhosphoSitePlus; P09327; -.
DR BioMuta; VIL1; -.
DR DMDM; 224471905; -.
DR EPD; P09327; -.
DR jPOST; P09327; -.
DR MassIVE; P09327; -.
DR MaxQB; P09327; -.
DR PaxDb; P09327; -.
DR PeptideAtlas; P09327; -.
DR PRIDE; P09327; -.
DR ProteomicsDB; 52213; -. [P09327-1]
DR ProteomicsDB; 75954; -.
DR Antibodypedia; 1531; 702 antibodies from 41 providers.
DR DNASU; 7429; -.
DR Ensembl; ENST00000248444.10; ENSP00000248444.5; ENSG00000127831.11. [P09327-1]
DR Ensembl; ENST00000440053.1; ENSP00000409270.1; ENSG00000127831.11. [P09327-2]
DR GeneID; 7429; -.
DR KEGG; hsa:7429; -.
DR MANE-Select; ENST00000248444.10; ENSP00000248444.5; NM_007127.3; NP_009058.2.
DR UCSC; uc002via.4; human. [P09327-1]
DR CTD; 7429; -.
DR DisGeNET; 7429; -.
DR GeneCards; VIL1; -.
DR HGNC; HGNC:12690; VIL1.
DR HPA; ENSG00000127831; Tissue enriched (intestine).
DR MIM; 193040; gene.
DR neXtProt; NX_P09327; -.
DR OpenTargets; ENSG00000127831; -.
DR PharmGKB; PA37309; -.
DR VEuPathDB; HostDB:ENSG00000127831; -.
DR eggNOG; KOG0443; Eukaryota.
DR GeneTree; ENSGT00940000160544; -.
DR HOGENOM; CLU_002568_3_1_1; -.
DR InParanoid; P09327; -.
DR OMA; FNWDYSK; -.
DR PhylomeDB; P09327; -.
DR TreeFam; TF313468; -.
DR PathwayCommons; P09327; -.
DR SignaLink; P09327; -.
DR SIGNOR; P09327; -.
DR BioGRID-ORCS; 7429; 10 hits in 1065 CRISPR screens.
DR ChiTaRS; VIL1; human.
DR EvolutionaryTrace; P09327; -.
DR GenomeRNAi; 7429; -.
DR Pharos; P09327; Tbio.
DR PRO; PR:P09327; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P09327; protein.
DR Bgee; ENSG00000127831; Expressed in jejunal mucosa and 116 other tissues.
DR ExpressionAtlas; P09327; baseline and differential.
DR Genevisible; P09327; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0032432; C:actin filament bundle; IDA:UniProtKB.
DR GO; GO:0005903; C:brush border; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0032433; C:filopodium tip; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035727; F:lysophosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0051693; P:actin filament capping; IDA:UniProtKB.
DR GO; GO:0030042; P:actin filament depolymerization; IDA:UniProtKB.
DR GO; GO:0030041; P:actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0051014; P:actin filament severing; IDA: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; IMP:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IEA:Ensembl.
DR GO; GO:0060327; P:cytoplasmic actin-based contraction involved in cell motility; IDA:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProtKB.
DR GO; GO:0001951; P:intestinal D-glucose absorption; IEA:Ensembl.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; IDA:UniProtKB.
DR GO; GO:0030836; P:positive regulation of actin filament depolymerization; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IDA:UniProtKB.
DR GO; GO:2000394; P:positive regulation of lamellipodium morphogenesis; IMP:UniProtKB.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0051125; P:regulation of actin nucleation; IDA:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB.
DR GO; GO:2000392; P:regulation of lamellipodium morphogenesis; ISS:UniProtKB.
DR GO; GO:0032532; P:regulation of microvillus length; IEA:Ensembl.
DR GO; GO:0061041; P:regulation of wound healing; ISS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IDA:UniProtKB.
DR GO; GO:1902896; P:terminal web assembly; IEA:Ensembl.
DR DisProt; DP02510; -.
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 3D-structure; Actin capping; Actin-binding; Alternative splicing;
KW Apoptosis; Calcium; Cell projection; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2846586"
FT CHAIN 2..827
FT /note="Villin-1"
FT /id="PRO_0000218727"
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 2..734
FT /note="Core"
FT REGION 2..126
FT /note="Necessary for homodimerization"
FT REGION 112..119
FT /note="LPA/PIP2-binding site 1"
FT REGION 138..146
FT /note="LPA/PIP2-binding site 2"
FT REGION 735..827
FT /note="Headpiece"
FT REGION 816..824
FT /note="LPA/PIP2-binding site 3"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62468"
FT VAR_SEQ 368..421
FT /note="AKVEQVKFDATSMHVKPQVAAQQKMVDDGSGEVQVWRIENLELVPVDSKWLG
FT HF -> GEGQAGAVREPGSRSWARRATWSTTHPPSLTCIFNEDFYAGSGLVLADGDVDK
FT L (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054436"
FT VAR_SEQ 422..827
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054437"
FT VARIANT 254
FT /note="K -> R (in dbSNP:rs35305540)"
FT /id="VAR_054502"
FT MUTAGEN 25
FT /note="E->Q: Inhibits activities regarding actin capping,
FT actin severing and actin bundling."
FT /evidence="ECO:0000269|PubMed:15272027"
FT MUTAGEN 44
FT /note="D->L: Inhibits activities regarding actin capping
FT and actin severing."
FT /evidence="ECO:0000269|PubMed:15272027"
FT MUTAGEN 46
FT /note="Y->F: Reduces activities regarding actin capping and
FT actin severing. Does not reduce lamellipodium or ruffle
FT localization and cell migration. Complete loss of
FT phosphorylation and interaction with PLCG1, does not reduce
FT lamellipodium or ruffle localization, inhibits cell
FT migration; when associated with F-60; F-81; F-256; F-286;
FT F-324; F-461; F-555; F-604 and F-725. Inhibits lamellipodia
FT localization but does not reduce interaction with PLCG1;
FT when associated with F-60; F-81 and F-256."
FT /evidence="ECO:0000269|PubMed:12269817,
FT ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 60
FT /note="Y->F: Reduces activities regarding actin capping and
FT actin severing, lamellipodium or ruffle localization and
FT cell migration. Complete loss of phosphorylation and
FT interaction with PLCG1, does not reduce lamellipodium or
FT ruffle localization, inhibits cell migration; when
FT associated with F-46; F-81; F-256; F-286; F-324; F-461; F-
FT 555; F-604 and F-725. Inhibits lamellipodia localization
FT but does not reduce interaction with PLCG1; when associated
FT with F-46; F-81 and F-256."
FT /evidence="ECO:0000269|PubMed:12269817,
FT ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 61
FT /note="D->N: Inhibits actin-severing activity. Does not
FT inhibit actin-nucleation and actin-capping activities."
FT /evidence="ECO:0000269|PubMed:15272027,
FT ECO:0000269|PubMed:17182858"
FT MUTAGEN 74
FT /note="E->L: Inhibits activities regarding actin capping
FT and actin severing."
FT /evidence="ECO:0000269|PubMed:15272027,
FT ECO:0000269|PubMed:17182858"
FT MUTAGEN 81
FT /note="Y->F: Reduces activities regarding actin nucleating
FT and actin severing, lamellipodium or ruffle localization
FT and cell migration. Complete loss of phosphorylation and
FT interaction with PLCG1, does not reduce lamellipodium or
FT ruffle localization, inhibits cell migration; when
FT associated with F-46; F-60; F-256; F-286; F-324; F-461; F-
FT 555; F-604 and F-725. Inhibits lamellipodia localization
FT but does not reduce interaction with PLCG1; when associated
FT with F-46; F-60 and F-256."
FT /evidence="ECO:0000269|PubMed:12269817,
FT ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 86..91
FT /note="DDFLKG->NTLLKE: Inhibits actin-severing activity and
FT motility of the S.flexneri, does not inhibit activities
FT regarding actin nucleation, actin capping and actin
FT bundling, lamellipodium or ruffle localization and cell
FT morphology; when associated with 125-A--S-129."
FT /evidence="ECO:0000269|PubMed:17182858"
FT MUTAGEN 86
FT /note="D->L: Inhibits actin-severing activity. Does not
FT inhibit actin-capping activity."
FT /evidence="ECO:0000269|PubMed:15272027"
FT MUTAGEN 93
FT /note="A->G: Inhibits actin-severing activity. Does not
FT inhibit actin-capping activity."
FT /evidence="ECO:0000269|PubMed:15272027"
FT MUTAGEN 125..129
FT /note="GMKHV->AMHKTS: Inhibits actin-severing activity and
FT motility of the S.flexneri, does not inhibit activities
FT regarding actin nucleation, actin capping and actin
FT bundling, lamellipodium or ruffle localization and cell
FT morphology; when associated with 86-N--E-91."
FT /evidence="ECO:0000269|PubMed:17182858"
FT MUTAGEN 138
FT /note="R->A: Reduces binding to PIP2."
FT /evidence="ECO:0000269|PubMed:14594952"
FT MUTAGEN 145
FT /note="K->A: Does not reduce binding to PIP2."
FT /evidence="ECO:0000269|PubMed:14594952"
FT MUTAGEN 146
FT /note="R->A: Does not reduce binding to PIP2."
FT /evidence="ECO:0000269|PubMed:14594952"
FT MUTAGEN 256
FT /note="Y->F: Reduces activities regarding actin nucleation
FT and actin severing, lamellipodium or ruffle localization
FT and cell migration. Complete loss of phosphorylation and
FT interaction with PLCG1, does not reduce lamellipodium or
FT ruffle localization, inhibits cell migration; when
FT associated with F-46; F-60; F-81; F-286; F-324; F-461; F-
FT 555; F-604 and F-725. Inhibits lamellipodia localization
FT but does not reduce interaction with PLCG1; when associated
FT with F-46; F-60 and F-81."
FT /evidence="ECO:0000269|PubMed:12269817,
FT ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 286
FT /note="Y->F: Reduces actin-severing activity and
FT interaction with PLCG1. Complete loss of phosphorylation
FT and interaction with PLCG1, does not reduce lamellipodium
FT or ruffle localization, inhibits cell migration; when
FT associated with F-46; F-60; F-81; F-256; F-324; F-461; F-
FT 555; F-604 and F-725. Inhibits interaction with PLCG1 and
FT lamellipodia localization; when associated with F-324; F-
FT 461; F-555; F-604 and F-725."
FT /evidence="ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 324
FT /note="Y->F: Complete loss of phosphorylation and
FT interaction with PLCG1, does not reduce lamellipodium or
FT ruffle localization, inhibits cell migration; when
FT associated with F-46; F-60; F-81; F-256; F-286; F-461; F-
FT 555; F-604 and F-725. Inhibits interaction with PLCG1 and
FT lamellipodia localization; when associated with F-286; F-
FT 461; F-555; F-604 and F-725."
FT /evidence="ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 461
FT /note="Y->F: Complete loss of phosphorylation and
FT interaction with PLCG1, does not reduce lamellipodium or
FT ruffle localization, inhibits cell migration; when
FT associated with F-46; F-60; F-81; F-256; F-286; F-324; F-
FT 555; F-604 and F-725. Inhibits interaction with PLCG1 and
FT lamellipodia localization; when associated with F-286; F-
FT 324; F-555; F-604 and F-725."
FT /evidence="ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 467
FT /note="D->L: Reduces the Ca(2+)-dependent actin-severing
FT activity."
FT /evidence="ECO:0000269|PubMed:15084600"
FT MUTAGEN 555
FT /note="Y->F: Complete loss of phosphorylation and
FT interaction with PLCG1, does not reduce lamellipodium or
FT ruffle localization, inhibits cell migration; when
FT associated with F-46; F-60; F-81; F-256; F-286; F-324; F-
FT 461; F-604 and F-725. Inhibits interaction with PLCG1 and
FT lamellipodia localization; when associated with F-286; F-
FT 324; F-461; F-604 and F-725."
FT /evidence="ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 604
FT /note="Y->F: Complete loss of phosphorylation and
FT interaction with PLCG1, does not reduce lamellipodium or
FT ruffle localization, inhibits cell migration; when
FT associated with F-46; F-60; F-81; F-256; F-286; F-324; F-
FT 461; F-555 and F-725. Inhibits interaction with PLCG1 and
FT lamellipodia localization; when associated with F-286; F-
FT 324; F-461; F-555 and F-725."
FT /evidence="ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 715
FT /note="D->L: Reduces the Ca(2+)-dependent actin-severing
FT activity."
FT /evidence="ECO:0000269|PubMed:15084600"
FT MUTAGEN 725
FT /note="Y->F: Complete loss of phosphorylation and
FT interaction with PLCG1, does not reduce lamellipodium or
FT ruffle localization, inhibits cell migration; when
FT associated with F-46; F-60; F-81; F-256; F-286; F-324; F-
FT 461; F-555 and F-604. Inhibits interaction with PLCG1 and
FT lamellipodia localization; when associated with F-286; F-
FT 324; F-461; F-555 and F-604."
FT /evidence="ECO:0000269|PubMed:16921170,
FT ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:18054784"
FT MUTAGEN 815
FT /note="W->A: Reduces interaction with F-actin."
FT /evidence="ECO:0000269|PubMed:15096633"
FT MUTAGEN 822
FT /note="K->A: Does not reduce binding to PIP2."
FT /evidence="ECO:0000269|PubMed:14594952"
FT MUTAGEN 824
FT /note="K->A: Does not reduce binding to PIP2."
FT /evidence="ECO:0000269|PubMed:14594952"
FT CONFLICT 146
FT /note="R -> K (in Ref. 2; BAG36454)"
FT /evidence="ECO:0000305"
FT CONFLICT 732
FT /note="L -> S (in Ref. 1; CAA31386 and 4; CAA28355)"
FT /evidence="ECO:0000305"
FT CONFLICT 735
FT /note="S -> L (in Ref. 1; CAA31386)"
FT /evidence="ECO:0000305"
FT STRAND 620..625
FT /evidence="ECO:0007829|PDB:3FG7"
FT STRAND 632..635
FT /evidence="ECO:0007829|PDB:3FG7"
FT HELIX 641..643
FT /evidence="ECO:0007829|PDB:3FG7"
FT STRAND 648..653
FT /evidence="ECO:0007829|PDB:3FG7"
FT STRAND 658..662
FT /evidence="ECO:0007829|PDB:3FG7"
FT HELIX 668..684
FT /evidence="ECO:0007829|PDB:3FG7"
FT STRAND 685..688
FT /evidence="ECO:0007829|PDB:3FG7"
FT STRAND 695..699
FT /evidence="ECO:0007829|PDB:3FG7"
FT HELIX 705..708
FT /evidence="ECO:0007829|PDB:3FG7"
FT HELIX 795..800
FT /evidence="ECO:0007829|PDB:1UNC"
FT HELIX 806..811
FT /evidence="ECO:0007829|PDB:1UNC"
FT HELIX 814..823
FT /evidence="ECO:0007829|PDB:1UNC"
SQ SEQUENCE 827 AA; 92695 MW; 96439B33B81E5F19 CRC64;
MTKLSAQVKG SLNITTPGLQ IWRIEAMQMV PVPSSTFGSF FDGDCYIILA IHKTASSLSY
DIHYWIGQDS SLDEQGAAAI YTTQMDDFLK GRAVQHREVQ GNESEAFRGY FKQGLVIRKG
GVASGMKHVE TNSYDVQRLL HVKGKRNVVA GEVEMSWKSF NRGDVFLLDL GKLIIQWNGP
ESTRMERLRG MTLAKEIRDQ ERGGRTYVGV VDGENELASP KLMEVMNHVL GKRRELKAAV
PDTVVEPALK AALKLYHVSD SEGNLVVREV ATRPLTQDLL SHEDCYILDQ GGLKIYVWKG
KKANEQEKKG AMSHALNFIK AKQYPPSTQV EVQNDGAESA VFQQLFQKWT ASNRTSGLGK
THTVGSVAKV EQVKFDATSM HVKPQVAAQQ KMVDDGSGEV QVWRIENLEL VPVDSKWLGH
FYGGDCYLLL YTYLIGEKQH YLLYVWQGSQ ASQDEITASA YQAVILDQKY NGEPVQIRVP
MGKEPPHLMS IFKGRMVVYQ GGTSRTNNLE TGPSTRLFQV QGTGANNTKA FEVPARANFL
NSNDVFVLKT QSCCYLWCGK GCSGDEREMA KMVADTISRT EKQVVVEGQE PANFWMALGG
KAPYANTKRL QEENLVITPR LFECSNKTGR FLATEIPDFN QDDLEEDDVF LLDVWDQVFF
WIGKHANEEE KKAAATTAQE YLKTHPSGRD PETPIIVVKQ GHEPPTFTGW FLAWDPFKWS
NTKSYEDLKA ELGNSRDWSQ ITAEVTSPKV DVFNANSNLS SGPLPIFPLE QLVNKPVEEL
PEGVDPSRKE EHLSIEDFTQ AFGMTPAAFS ALPRWKQQNL KKEKGLF
