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 27-MAR-2024, entry version 197. 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; 240. DR CORUM; O95425; -. DR IntAct; O95425; 101. DR MINT; O95425; -. DR STRING; 9606.ENSP00000348128; -. DR GlyGen; O95425; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000348128; -. DR PeptideAtlas; O95425; -. DR ProteomicsDB; 50866; -. [O95425-1] DR ProteomicsDB; 50867; -. [O95425-2] DR Pumba; O95425; -. 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 AGR; HGNC:11480; -. 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; MEQHKRA; -. DR OrthoDB; 2999535at2759; -. DR PhylomeDB; O95425; -. DR TreeFam; TF316081; -. DR PathwayCommons; O95425; -. DR SignaLink; O95425; -. DR SIGNOR; O95425; -. DR BioGRID-ORCS; 6840; 14 hits in 1153 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 193 other cell types or tissues. DR ExpressionAtlas; O95425; baseline and differential. 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:HPA. 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 CDD; cd11280; gelsolin_like; 1. DR CDD; cd11289; gelsolin_S2_like; 1. DR CDD; cd11293; gelsolin_S4_like; 1. DR CDD; cd11288; gelsolin_S5_like; 1. DR Gene3D; 3.40.20.10; Severin; 5. DR Gene3D; 1.10.950.10; Villin headpiece domain; 1. DR InterPro; IPR029006; ADF-H/Gelsolin-like_dom_sf. DR InterPro; IPR007123; Gelsolin-like_dom. DR InterPro; IPR007122; Villin/Gelsolin. DR InterPro; IPR003128; Villin_headpiece. DR InterPro; IPR036886; Villin_headpiece_dom_sf. DR PANTHER; PTHR11977:SF45; SUPERVILLIN; 1. DR PANTHER; PTHR11977; VILLIN; 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; SSF55753; Actin depolymerizing proteins; 5. DR SUPFAM; SSF47050; VHP, Villin headpiece domain; 1. DR PROSITE; PS51089; HP; 1. DR Genevisible; O95425; HS. 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 //