SVIL_HUMAN
ID SVIL_HUMAN Reviewed; 2214 AA.
AC O95425; D3DRW9; M1J557; O60611; O60612; Q5VZK5; Q5VZK6; Q9H1R7;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUL-2009, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Supervillin {ECO:0000303|PubMed:9867483};
DE AltName: Full=Archvillin {ECO:0000303|PubMed:12711699};
DE AltName: Full=p205/p250 {ECO:0000303|PubMed:12711699, ECO:0000303|PubMed:9867483};
GN Name=SVIL {ECO:0000303|PubMed:9867483};
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 2), VARIANTS ALA-189 AND ALA-1235,
RP INTERACTION WITH ACTIN, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma, and Kidney;
RX PubMed=9867483; DOI=10.1006/geno.1998.5466;
RA Pope R.K., Pestonjamasp K.N., Smith K.P., Wulfkuhle J.D., Strassel C.P.,
RA Lawrence J.B., Luna E.J.;
RT "Cloning, characterization, and chromosomal localization of human
RT supervillin (SVIL).";
RL Genomics 52:342-351(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1), AND VARIANTS
RP ALA-189; ILE-422 AND ALA-1235.
RX PubMed=12711699; DOI=10.1242/jcs.00422;
RA Oh S.W., Pope R.K., Smith K.P., Crowley J.L., Nebl T., Lawrence J.B.,
RA Luna E.J.;
RT "Archvillin, a muscle-specific isoform of supervillin, is an early
RT expressed component of the costameric membrane skeleton.";
RL J. Cell Sci. 116:2261-2275(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SV4), AND ALTERNATIVE SPLICING
RP (ISOFORMS SV3 AND SV4).
RX PubMed=23382381; DOI=10.1074/jbc.m112.416842;
RA Fang Z., Luna E.J.;
RT "Supervillin-mediated suppression of p53 protein enhances cell survival.";
RL J. Biol. Chem. 288:7918-7929(2013).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-422.
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-221 AND SER-245,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-270 (ISOFORMS 2 AND SV3), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-852, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [8]
RP INTERACTION WITH NEB.
RX PubMed=18639526; DOI=10.1016/j.bbrc.2008.07.036;
RA Lee M.-A., Joo Y.M., Lee Y.M., Kim H.S., Kim J.-H., Choi J.-K., Ahn S.-J.,
RA Min B.-I., Kim C.-R.;
RT "Archvillin anchors in the Z-line of skeletal muscle via the nebulin C-
RT terminus.";
RL Biochem. Biophys. Res. Commun. 374:320-324(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-270 (ISOFORMS 2 AND SV3), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-270, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50; SER-221; SER-245;
RP SER-920; THR-1111; SER-1120; SER-1225 AND SER-1322, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-261 AND SER-270 (ISOFORMS 2 AND SV3), VARIANT [LARGE
RP SCALE ANALYSIS] ALA-1235, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP FUNCTION (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=19109420; DOI=10.1091/mbc.e08-08-0867;
RA Crowley J.L., Smith T.C., Fang Z., Takizawa N., Luna E.J.;
RT "Supervillin reorganizes the actin cytoskeleton and increases invadopodial
RT efficiency.";
RL Mol. Biol. Cell 20:948-962(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50; SER-221; SER-245;
RP SER-270; SER-707; SER-914; SER-920; SER-924; SER-968; SER-1120; SER-1225;
RP THR-1230 AND SER-1322, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261
RP AND SER-270 (ISOFORMS 2 AND SV3), VARIANT [LARGE SCALE ANALYSIS] ALA-1235,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245; SER-707; SER-914 AND
RP SER-968, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261 AND SER-270
RP (ISOFORMS 2 AND SV3), VARIANT [LARGE SCALE ANALYSIS] ALA-1235, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50; SER-221; SER-245;
RP SER-707; THR-852; SER-920; SER-968 AND SER-1120, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-240; SER-245; SER-253;
RP SER-270; SER-769; SER-920; SER-1225 AND SER-1322, 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 [18]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1203, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [19]
RP INVOLVEMENT IN MFM10, VARIANT MFM10 1604-TYR--PHE-2214 DEL, AND
RP CHARACTERIZATION OF VARIANT MFM10 1604-TYR--PHE-2214 DEL.
RX PubMed=32779703; DOI=10.1093/brain/awaa206;
RA Hedberg-Oldfors C., Meyer R., Nolte K., Abdul Rahim Y., Lindberg C.,
RA Karason K., Thuestad I.J., Visuttijai K., Geijer M., Begemann M., Kraft F.,
RA Lausberg E., Hitpass L., Goetzl R., Luna E.J., Lochmueller H.,
RA Koschmieder S., Gramlich M., Gess B., Elbracht M., Weis J., Kurth I.,
RA Oldfors A., Knopp C.;
RT "Loss of supervillin causes myopathy with myofibrillar disorganization and
RT autophagic vacuoles.";
RL Brain 143:2406-2420(2020).
RN [20]
RP STRUCTURE BY NMR OF 2149-2214, AND MUTAGENESIS OF LEU-2176.
RX PubMed=19683541; DOI=10.1016/j.jmb.2009.08.018;
RA Brown J.W., Vardar-Ulu D., McKnight C.J.;
RT "How to arm a supervillin: designing F-actin binding activity into
RT supervillin headpiece.";
RL J. Mol. Biol. 393:608-618(2009).
CC -!- FUNCTION: [Isoform 1]: Forms a high-affinity link between the actin
CC cytoskeleton and the membrane. Is among the first costameric proteins
CC to assemble during myogenesis and it contributes to myogenic membrane
CC structure and differentiation (PubMed:12711699). Appears to be involved
CC in myosin II assembly. May modulate myosin II regulation through MLCK
CC during cell spreading, an initial step in cell migration. May play a
CC role in invadopodial function (PubMed:19109420).
CC {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.
CC -!- FUNCTION: [Isoform 2]: May be involved in modulation of focal
CC adhesions. Supervillin-mediated down-regulation of focal adhesions
CC involves binding to TRIP6. Plays a role in cytokinesis through KIF14
CC interaction (By similarity). {ECO:0000250|UniProtKB:O46385}.
CC -!- SUBUNIT: Associates with F-actin (PubMed:9867483). Interacts with NEB
CC (PubMed:18639526). Interacts with MYH9 (By similarity). Interacts with
CC MYLK (By similarity). Interacts with TASOR (By similarity).
CC {ECO:0000250|UniProtKB:O46385, ECO:0000250|UniProtKB:Q8K4L3,
CC ECO:0000269|PubMed:18639526, ECO:0000269|PubMed:9867483}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with TRIP6 (By similarity). Interacts
CC with DYNLT1 (By similarity). Interacts with KIF14; at midbody during
CC cytokinesis (By similarity). {ECO:0000250|UniProtKB:O46385}.
CC -!- INTERACTION:
CC O95425; P20929: NEB; NbExp=4; IntAct=EBI-487145, EBI-1049657;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side. Cytoplasm, cytoskeleton. Cell projection,
CC invadopodium. Cell projection, podosome. Midbody
CC {ECO:0000250|UniProtKB:O46385}. Cleavage furrow
CC {ECO:0000250|UniProtKB:O46385}. Note=Tightly associated with both actin
CC filaments and plasma membranes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Archvillin {ECO:0000303|PubMed:12711699}, p250
CC {ECO:0000303|PubMed:12711699}, SV2;
CC IsoId=O95425-1; Sequence=Displayed;
CC Name=2; Synonyms=Supervillin {ECO:0000303|PubMed:9867483}, p205
CC {ECO:0000303|PubMed:9867483}, SV1;
CC IsoId=O95425-2; Sequence=VSP_012425, VSP_012426;
CC Name=SV3;
CC IsoId=O95425-3; Sequence=VSP_053768;
CC Name=SV4;
CC IsoId=O95425-4; Sequence=VSP_012426;
CC -!- TISSUE SPECIFICITY: Expressed in many tissues. Most abundant in muscle,
CC bone marrow, thyroid gland and salivary gland. Isoform 1 (archvillin)
CC is muscle specific. {ECO:0000269|PubMed:9867483}.
CC -!- DOMAIN: As opposed to other villin-type headpiece domains, supervillin
CC HP (SVHP) doesn't bind F-actin due to the absence of a conformationally
CC flexible region (V-loop). {ECO:0000269|PubMed:19683541}.
CC -!- DISEASE: Myopathy, myofibrillar, 10 (MFM10) [MIM:619040]: A form of
CC myofibrillar myopathy, a group of chronic neuromuscular disorders
CC characterized at ultrastructural level by disintegration of the
CC sarcomeric Z disk and myofibrils, and replacement of the normal
CC myofibrillar markings by small dense granules, or larger hyaline
CC masses, or amorphous material. MFM10 is an autosomal recessive disorder
CC characterized by muscle pain, cramping, exercise fatigue, and
CC progressive muscle rigidity. {ECO:0000269|PubMed:32779703}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the villin/gelsolin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF051850; AAC64695.1; -; mRNA.
DR EMBL; AF051851; AAC64696.1; -; mRNA.
DR EMBL; AF109135; AAD14682.1; -; mRNA.
DR EMBL; JX467682; AGE81989.1; -; mRNA.
DR EMBL; AL158167; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471072; EAW86018.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86019.1; -; Genomic_DNA.
DR CCDS; CCDS7163.1; -. [O95425-2]
DR CCDS; CCDS7164.1; -. [O95425-1]
DR RefSeq; NP_003165.2; NM_003174.3. [O95425-2]
DR RefSeq; NP_068506.2; NM_021738.2. [O95425-1]
DR PDB; 2K6M; NMR; -; S=2149-2214.
DR PDB; 2K6N; NMR; -; A=2149-2214.
DR PDBsum; 2K6M; -.
DR PDBsum; 2K6N; -.
DR AlphaFoldDB; O95425; -.
DR BMRB; O95425; -.
DR SMR; O95425; -.
DR BioGRID; 112707; 203.
DR CORUM; O95425; -.
DR IntAct; O95425; 88.
DR MINT; O95425; -.
DR STRING; 9606.ENSP00000348128; -.
DR GlyGen; O95425; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95425; -.
DR PhosphoSitePlus; O95425; -.
DR BioMuta; SVIL; -.
DR CPTAC; CPTAC-1641; -.
DR EPD; O95425; -.
DR jPOST; O95425; -.
DR MassIVE; O95425; -.
DR MaxQB; O95425; -.
DR PaxDb; O95425; -.
DR PeptideAtlas; O95425; -.
DR PRIDE; O95425; -.
DR ProteomicsDB; 50866; -. [O95425-1]
DR ProteomicsDB; 50867; -. [O95425-2]
DR ABCD; O95425; 5 sequenced antibodies.
DR Antibodypedia; 4390; 121 antibodies from 21 providers.
DR CPTC; O95425; 4 antibodies.
DR DNASU; 6840; -.
DR Ensembl; ENST00000355867.9; ENSP00000348128.4; ENSG00000197321.16. [O95425-1]
DR Ensembl; ENST00000375398.6; ENSP00000364547.3; ENSG00000197321.16. [O95425-4]
DR Ensembl; ENST00000375400.7; ENSP00000364549.3; ENSG00000197321.16. [O95425-2]
DR GeneID; 6840; -.
DR KEGG; hsa:6840; -.
DR MANE-Select; ENST00000355867.9; ENSP00000348128.4; NM_021738.3; NP_068506.2.
DR UCSC; uc001iut.2; human. [O95425-1]
DR CTD; 6840; -.
DR DisGeNET; 6840; -.
DR GeneCards; SVIL; -.
DR HGNC; HGNC:11480; SVIL.
DR HPA; ENSG00000197321; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; SVIL; -.
DR MIM; 604126; gene.
DR MIM; 619040; phenotype.
DR neXtProt; NX_O95425; -.
DR OpenTargets; ENSG00000197321; -.
DR PharmGKB; PA36265; -.
DR VEuPathDB; HostDB:ENSG00000197321; -.
DR eggNOG; KOG0445; Eukaryota.
DR GeneTree; ENSGT00940000154653; -.
DR HOGENOM; CLU_001547_1_0_1; -.
DR InParanoid; O95425; -.
DR OMA; KGGMVIH; -.
DR OrthoDB; 1376537at2759; -.
DR PhylomeDB; O95425; -.
DR TreeFam; TF316081; -.
DR PathwayCommons; O95425; -.
DR SignaLink; O95425; -.
DR BioGRID-ORCS; 6840; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; SVIL; human.
DR EvolutionaryTrace; O95425; -.
DR GeneWiki; SVIL; -.
DR GenomeRNAi; 6840; -.
DR Pharos; O95425; Tbio.
DR PRO; PR:O95425; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; O95425; protein.
DR Bgee; ENSG00000197321; Expressed in gluteal muscle and 191 other tissues.
DR ExpressionAtlas; O95425; baseline and differential.
DR Genevisible; O95425; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0032154; C:cleavage furrow; ISS:UniProtKB.
DR GO; GO:0043034; C:costamere; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0036449; C:microtubule minus-end; ISS:UniProtKB.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0002102; C:podosome; IEA:UniProtKB-SubCell.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IBA:GO_Central.
DR GO; GO:0051014; P:actin filament severing; IBA:GO_Central.
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:0032467; P:positive regulation of cytokinesis; ISS:UniProtKB.
DR GO; GO:0007519; P:skeletal muscle tissue development; IMP:UniProtKB.
DR Gene3D; 1.10.950.10; -; 1.
DR Gene3D; 3.40.20.10; -; 5.
DR InterPro; IPR029006; ADF-H/Gelsolin-like_dom_sf.
DR InterPro; IPR007123; Gelsolin-like_dom.
DR InterPro; IPR015628; SV/p205.
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:SF86; PTHR11977:SF86; 1.
DR Pfam; PF00626; Gelsolin; 1.
DR Pfam; PF02209; VHP; 1.
DR PRINTS; PR00597; GELSOLIN.
DR SMART; SM00262; GEL; 4.
DR SMART; SM00153; VHP; 1.
DR SUPFAM; SSF47050; SSF47050; 1.
DR PROSITE; PS51089; HP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Calcium; Cell junction;
KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Desmin-related myopathy; Disease variant; Membrane; Methylation;
KW Myofibrillar myopathy; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..2214
FT /note="Supervillin"
FT /id="PRO_0000218740"
FT REPEAT 1441..1540
FT /note="Gelsolin-like 1"
FT REPEAT 1560..1682
FT /note="Gelsolin-like 2"
FT REPEAT 1752..1862
FT /note="Gelsolin-like 3"
FT REPEAT 1881..1982
FT /note="Gelsolin-like 4"
FT REPEAT 2015..2122
FT /note="Gelsolin-like 5"
FT DOMAIN 2151..2214
FT /note="HP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00595"
FT REGION 1..174
FT /note="Interaction with MYLK"
FT /evidence="ECO:0000250"
FT REGION 36..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 346..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 396..447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 460..584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 608..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 781..810
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1145..1166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1419..1687
FT /note="Interaction with NEB"
FT /evidence="ECO:0000269|PubMed:18639526"
FT COMPBIAS 53..68
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..96
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..161
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 205..266
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 305..319
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..444
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 631..687
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 238
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L3"
FT MOD_RES 240
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L3"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L3"
FT MOD_RES 673
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L3"
FT MOD_RES 707
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 769
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 850
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L3"
FT MOD_RES 852
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 914
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 920
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 924
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 968
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 1000
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L3"
FT MOD_RES 1052
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L3"
FT MOD_RES 1111
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1120
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1203
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 1225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"
FT MOD_RES 1230
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1234
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L3"
FT MOD_RES 1322
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"
FT MOD_RES 1405
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L3"
FT VAR_SEQ 276..669
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9867483"
FT /id="VSP_012425"
FT VAR_SEQ 276..302
FT /note="Missing (in isoform SV3)"
FT /evidence="ECO:0000305"
FT /id="VSP_053768"
FT VAR_SEQ 750..781
FT /note="Missing (in isoform 2 and isoform SV4)"
FT /evidence="ECO:0000303|PubMed:23382381,
FT ECO:0000303|PubMed:9867483"
FT /id="VSP_012426"
FT VARIANT 189
FT /note="V -> A (in dbSNP:rs10160013)"
FT /evidence="ECO:0000269|PubMed:12711699,
FT ECO:0000269|PubMed:9867483"
FT /id="VAR_020791"
FT VARIANT 422
FT /note="V -> I (in dbSNP:rs1247696)"
FT /evidence="ECO:0000269|PubMed:12711699, ECO:0000269|Ref.5"
FT /id="VAR_058308"
FT VARIANT 1041
FT /note="V -> L (in dbSNP:rs7070135)"
FT /id="VAR_057467"
FT VARIANT 1235
FT /note="P -> A (in dbSNP:rs2368406)"
FT /evidence="ECO:0000269|PubMed:12711699,
FT ECO:0000269|PubMed:9867483, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT /id="VAR_020792"
FT VARIANT 1604..2214
FT /note="Missing (in MFM10; decreased protein abundance)"
FT /evidence="ECO:0000269|PubMed:32779703"
FT /id="VAR_085140"
FT VARIANT 1688
FT /note="S -> P (in dbSNP:rs11007612)"
FT /id="VAR_024691"
FT VARIANT 2005
FT /note="I -> V (in dbSNP:rs7921306)"
FT /id="VAR_057468"
FT VARIANT 2041
FT /note="A -> V (in dbSNP:rs17694739)"
FT /id="VAR_057469"
FT MUTAGEN 2176
FT /note="L->K: Strongly increased affinity for F-actin."
FT /evidence="ECO:0000269|PubMed:19683541"
FT HELIX 2159..2162
FT /evidence="ECO:0007829|PDB:2K6M"
FT STRAND 2169..2172
FT /evidence="ECO:0007829|PDB:2K6M"
FT HELIX 2177..2179
FT /evidence="ECO:0007829|PDB:2K6M"
FT HELIX 2182..2188
FT /evidence="ECO:0007829|PDB:2K6M"
FT STRAND 2189..2191
FT /evidence="ECO:0007829|PDB:2K6M"
FT HELIX 2193..2196
FT /evidence="ECO:0007829|PDB:2K6M"
FT HELIX 2201..2211
FT /evidence="ECO:0007829|PDB:2K6M"
FT MOD_RES O95425-2:261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES O95425-2:270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES O95425-3:261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES O95425-3:270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
SQ SEQUENCE 2214 AA; 247746 MW; 6C4793D31FCBDF7C CRC64;
MKRKERIARR LEGIENDTQP ILLQSCTGLV THRLLEEDTP RYMRASDPAS PHIGRSNEEE
ETSDSSLEKQ TRSKYCTETS GVHGDSPYGS GTMDTHSLES KAERIARYKA ERRRQLAEKY
GLTLDPEADS EYLSRYTKSR KEPDAVEKRG GKSDKQEESS RDASSLYPGT ETMGLRTCAG
ESKDYALHVG DGSSDPEVLL NIENQRRGQE LSATRQAHDL SPAAESSSTF SFSGRDSSFT
EVPRSPKHAH SSSLQQAASR SPSFGDPQLS PEARPSTGKP KHEWFLQKDS EGDTPSLINW
PSRVKVREKL VKEESARNSP ELASESVTQR RHQPAPVHYV SFQSEHSAFD RVPSKAAGST
RQPIRGYVQP ADTGHTAKLV TPETPENASE CSWVASATQN VPKPPSLTVL EGDGRDSPVL
HVCESKAEEE EGEGEGEEKE EDVCFTEALE QSKKTLLALE GDGLVRSPED PSRNEDFGKP
AVSTVTLEHQ KELENVAQPP QAPHQPTERT GRSEMVLYIQ SEPVSQDAKP TGHNREASKK
RKVRTRSLSD FTGPPQLQAL KYKDPASRRE LELPSSKTEG PYGEISMLDT KVSVAQLRSA
FLASANACRR PELKSRVERS AEGPGLPTGV ERERGSRKPR RYFSPGESRK TSERFRTQPI
TSAERKESDR CTSHSETPTV DDEEKVDERA KLSVAAKRLL FREMEKSFDE QNVPKRRSRN
TAVEQRLRRL QDRSLTQPIT TEEVVIAATE PIPASCSGGT HPVMARLPSP TVARSAVQPA
RLQASAHQKA LAKDQTNEGK ELAEQGEPDS STLSLAEKLA LFNKLSQPVS KAISTRNRID
TRQRRMNARY QTQPVTLGEV EQVQSGKLIP FSPAVNTSVS TVASTVAPMY AGDLRTKPPL
DHNASATDYK FSSSIENSDS PVRSILKSQA WQPLVEGSEN KGMLREYGET ESKRALTGRD
SGMEKYGSFE EAEASYPILN RAREGDSHKE SKYAVPRRGS LERANPPITH LGDEPKEFSM
AKMNAQGNLD LRDRLPFEEK VEVENVMKRK FSLRAAEFGE PTSEQTGTAA GKTIAQTTAP
VSWKPQDSSE QPQEKLCKNP CAMFAAGEIK TPTGEGLLDS PSKTMSIKER LALLKKSGEE
DWRNRLSRRQ EGGKAPASSL HTQEAGRSLI KKRVTESRES QMTIEERKQL ITVREEAWKT
RGRGAANDST QFTVAGRMVK KGLASPTAIT PVASPICGKT RGTTPVSKPL EDIEARPDMQ
LESDLKLDRL ETFLRRLNNK VGGMHETVLT VTGKSVKEVM KPDDDETFAK FYRSVDYNMP
RSPVEMDEDF DVIFDPYAPK LTSSVAEHKR AVRPKRRVQA SKNPLKMLAA REDLLQEYTE
QRLNVAFMES KRMKVEKMSS NSNFSEVTLA GLASKENFSN VSLRSVNLTE QNSNNSAVPY
KRLMLLQIKG RRHVQTRLVE PRASALNSGD CFLLLSPHCC FLWVGEFANV IEKAKASELA
TLIQTKRELG CRATYIQTIE EGINTHTHAA KDFWKLLGGQ TSYQSAGDPK EDELYEAAII
ETNCIYRLMD DKLVPDDDYW GKIPKCSLLQ PKEVLVFDFG SEVYVWHGKE VTLAQRKIAF
QLAKHLWNGT FDYENCDINP LDPGECNPLI PRKGQGRPDW AIFGRLTEHN ETILFKEKFL
DWTELKRSNE KNPGELAQHK EDPRTDVKAY DVTRMVSMPQ TTAGTILDGV NVGRGYGLVE
GHDRRQFEIT SVSVDVWHIL EFDYSRLPKQ SIGQFHEGDA YVVKWKFMVS TAVGSRQKGE
HSVRAAGKEK CVYFFWQGRH STVSEKGTSA LMTVELDEER GAQVQVLQGK EPPCFLQCFQ
GGMVVHSGRR EEEEENVQSE WRLYCVRGEV PVEGNLLEVA CHCSSLRSRT SMVVLNVNKA
LIYLWHGCKA QAHTKEVGRT AANKIKEQCP LEAGLHSSSK VTIHECDEGS EPLGFWDALG
RRDRKAYDCM LQDPGSFNFA PRLFILSSSS GDFAATEFVY PARAPSVVSS MPFLQEDLYS
APQPALFLVD NHHEVYLWQG WWPIENKITG SARIRWASDR KSAMETVLQY CKGKNLKKPA
PKSYLIHAGL EPLTFTNMFP SWEHREDIAE ITEMDTEVSN QITLVEDVLA KLCKTIYPLA
DLLARPLPEG VDPLKLEIYL TDEDFEFALD MTRDEYNALP AWKQVNLKKA KGLF
