ID   VILL_HUMAN              Reviewed;         856 AA.
AC   O15195; A8MZP1; Q9BT80; Q9BWH7;
DT   20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2005, sequence version 3.
DT   27-MAR-2024, entry version 182.
DE   RecName: Full=Villin-like protein;
GN   Name=VILL;
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 [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA   Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 127-856 (ISOFORM 1).
RC   TISSUE=Eye, and Pancreas;
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 171-856 (ISOFORM 1).
RC   TISSUE=Fetal brain, Lung, and Pancreas;
RX   PubMed=9179494; DOI=10.1093/dnares/4.1.35;
RA   Ishikawa S., Kai M., Tamari M., Takei Y., Takeuchi K., Bandou H.,
RA   Yamane Y., Ogawa M., Nakamura Y.;
RT   "Sequence analysis of a 685-kb genomic region on chromosome 3p22-p21.3 that
RT   is homozygously deleted in a lung carcinoma cell line.";
RL   DNA Res. 4:35-43(1997).
RN   [5]
RP   VARIANT GLN-798.
RX   PubMed=29846532; DOI=10.1093/brain/awy129;
RA   Sagie S., Lerman-Sagie T., Maljevic S., Yosovich K., Detert K., Chung S.K.,
RA   Rees M.I., Lerche H., Lev D.;
RT   "Expanding the phenotype of TRAK1 mutations: hyperekplexia and refractory
RT   status epilepticus.";
RL   Brain 141:E55-E55(2018).
CC   -!- FUNCTION: Possible tumor suppressor.
CC   -!- INTERACTION:
CC       O15195-2; Q99732: LITAF; NbExp=3; IntAct=EBI-21845957, EBI-725647;
CC       O15195-2; P10636: MAPT; NbExp=3; IntAct=EBI-21845957, EBI-366182;
CC       O15195-2; Q96CV9: OPTN; NbExp=3; IntAct=EBI-21845957, EBI-748974;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O15195-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O15195-2; Sequence=VSP_006729;
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed in 16 tissues examined.
CC   -!- SIMILARITY: Belongs to the villin/gelsolin family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH00243.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAH04300.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AC105752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471055; EAW64506.1; -; Genomic_DNA.
DR   EMBL; BC000243; AAH00243.1; ALT_INIT; mRNA.
DR   EMBL; BC004300; AAH04300.1; ALT_INIT; mRNA.
DR   EMBL; D88154; BAA21668.1; -; mRNA.
DR   CCDS; CCDS2670.2; -. [O15195-1]
DR   PIR; JC5708; JC5708.
DR   RefSeq; NP_056957.3; NM_015873.3. [O15195-1]
DR   RefSeq; XP_005265248.1; XM_005265191.3.
DR   RefSeq; XP_005265249.1; XM_005265192.4.
DR   RefSeq; XP_006713247.1; XM_006713184.3.
DR   RefSeq; XP_011532072.1; XM_011533770.2.
DR   AlphaFoldDB; O15195; -.
DR   SMR; O15195; -.
DR   BioGRID; 119155; 8.
DR   IntAct; O15195; 9.
DR   STRING; 9606.ENSP00000283713; -.
DR   GlyGen; O15195; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O15195; -.
DR   PhosphoSitePlus; O15195; -.
DR   BioMuta; VILL; -.
DR   EPD; O15195; -.
DR   jPOST; O15195; -.
DR   MassIVE; O15195; -.
DR   MaxQB; O15195; -.
DR   PaxDb; 9606-ENSP00000283713; -.
DR   PeptideAtlas; O15195; -.
DR   ProteomicsDB; 48500; -. [O15195-1]
DR   ProteomicsDB; 48501; -. [O15195-2]
DR   Antibodypedia; 48930; 112 antibodies from 21 providers.
DR   DNASU; 50853; -.
DR   Ensembl; ENST00000283713.10; ENSP00000283713.6; ENSG00000136059.16. [O15195-1]
DR   Ensembl; ENST00000383759.7; ENSP00000373266.2; ENSG00000136059.16. [O15195-1]
DR   GeneID; 50853; -.
DR   KEGG; hsa:50853; -.
DR   MANE-Select; ENST00000383759.7; ENSP00000373266.2; NM_015873.4; NP_056957.3.
DR   UCSC; uc003chj.4; human. [O15195-1]
DR   AGR; HGNC:30906; -.
DR   CTD; 50853; -.
DR   DisGeNET; 50853; -.
DR   GeneCards; VILL; -.
DR   HGNC; HGNC:30906; VILL.
DR   HPA; ENSG00000136059; Group enriched (intestine, stomach).
DR   MIM; 619666; gene.
DR   neXtProt; NX_O15195; -.
DR   OpenTargets; ENSG00000136059; -.
DR   PharmGKB; PA134911684; -.
DR   VEuPathDB; HostDB:ENSG00000136059; -.
DR   eggNOG; KOG0443; Eukaryota.
DR   GeneTree; ENSGT00940000160253; -.
DR   HOGENOM; CLU_002568_3_1_1; -.
DR   InParanoid; O15195; -.
DR   OMA; CWEGVHS; -.
DR   OrthoDB; 25995at2759; -.
DR   PhylomeDB; O15195; -.
DR   TreeFam; TF313468; -.
DR   PathwayCommons; O15195; -.
DR   SignaLink; O15195; -.
DR   BioGRID-ORCS; 50853; 11 hits in 1153 CRISPR screens.
DR   ChiTaRS; VILL; human.
DR   GenomeRNAi; 50853; -.
DR   Pharos; O15195; Tbio.
DR   PRO; PR:O15195; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; O15195; Protein.
DR   Bgee; ENSG00000136059; Expressed in mucosa of transverse colon and 114 other cell types or tissues.
DR   ExpressionAtlas; O15195; baseline and differential.
DR   GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR   GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IBA:GO_Central.
DR   GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
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   CDD; cd11290; gelsolin_S1_like; 1.
DR   CDD; cd11289; gelsolin_S2_like; 1.
DR   CDD; cd11292; gelsolin_S3_like; 1.
DR   CDD; cd11293; gelsolin_S4_like; 1.
DR   CDD; cd11288; gelsolin_S5_like; 1.
DR   CDD; cd11291; gelsolin_S6_like; 1.
DR   Gene3D; 3.40.20.10; Severin; 6.
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; IPR036180; Gelsolin-like_dom_sf.
DR   InterPro; IPR007122; Villin/Gelsolin.
DR   InterPro; IPR003128; Villin_headpiece.
DR   InterPro; IPR036886; Villin_headpiece_dom_sf.
DR   PANTHER; PTHR11977; VILLIN; 1.
DR   PANTHER; PTHR11977:SF30; VILLIN-LIKE PROTEIN; 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; SSF55753; Actin depolymerizing proteins; 4.
DR   SUPFAM; SSF82754; C-terminal, gelsolin-like domain of Sec23/24; 2.
DR   SUPFAM; SSF47050; VHP, Villin headpiece domain; 1.
DR   PROSITE; PS51089; HP; 1.
DR   Genevisible; O15195; HS.
PE   1: Evidence at protein level;
KW   Actin capping; Actin-binding; Alternative splicing; Calcium;
KW   Reference proteome; Repeat.
FT   CHAIN           1..856
FT                   /note="Villin-like protein"
FT                   /id="PRO_0000218738"
FT   REPEAT          22..74
FT                   /note="Gelsolin-like 1"
FT   REPEAT          146..186
FT                   /note="Gelsolin-like 2"
FT   REPEAT          263..307
FT                   /note="Gelsolin-like 3"
FT   REPEAT          401..450
FT                   /note="Gelsolin-like 4"
FT   REPEAT          521..561
FT                   /note="Gelsolin-like 5"
FT   REPEAT          624..665
FT                   /note="Gelsolin-like 6"
FT   DOMAIN          790..856
FT                   /note="HP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00595"
FT   REGION          762..796
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        762..795
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         262..275
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_006729"
FT   VARIANT         610
FT                   /note="F -> L (in dbSNP:rs1892814)"
FT                   /id="VAR_052938"
FT   VARIANT         740
FT                   /note="L -> F (in dbSNP:rs9816693)"
FT                   /id="VAR_052939"
FT   VARIANT         798
FT                   /note="R -> Q (in dbSNP:rs147292695)"
FT                   /evidence="ECO:0000269|PubMed:29846532"
FT                   /id="VAR_081640"
FT   CONFLICT        229
FT                   /note="R -> C (in Ref. 4; BAA21668)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   856 AA;  95907 MW;  A8B7EDEFDF11CEE1 CRC64;
     MDISKGLPGM QGGLHIWISE NRKMVPVPEG AYGNFFEEHC YVILHVPQSP KATQGASSDL
     HYWVGKQAGA EAQGAAEAFQ QRLQDELGGQ TVLHREAQGH ESDCFCSYFR PGIIYRKGGL
     ASDLKHVETN LFNIQRLLHI KGRKHVSATE VELSWNSFNK GDIFLLDLGK MMIQWNGPKT
     SISEKARGLA LTYSLRDRER GGGRAQIGVV DDEAKAPDLM QIMEAVLGRR VGSLRAATPS
     KDINQLQKAN VRLYHVYEKG KDLVVLELAT PPLTQDLLQE EDFYILDQGG FKIYVWQGRM
     SSLQERKAAF SRAVGFIQAK GYPTYTNVEV VNDGAESAAF KQLFRTWSEK RRRNQKLGGR
     DKSIHVKLDV GKLHTQPKLA AQLRMVDDGS GKVEVWCIQD LHRQPVDPKR HGQLCAGNCY
     LVLYTYQRLG RVQYILYLWQ GHQATADEIE ALNSNAEELD VMYGGVLVQE HVTMGSEPPH
     FLAIFQGQLV IFQERAGHHG KGQSASTTRL FQVQGTDSHN TRTMEVPARA SSLNSSDIFL
     LVTASVCYLW FGKGCNGDQR EMARVVVTVI SRKNEETVLE GQEPPHFWEA LGGRAPYPSN
     KRLPEEVPSF QPRLFECSSH MGCLVLAEVG FFSQEDLDKY DIMLLDTWQE IFLWLGEAAS
     EWKEAVAWGQ EYLKTHPAGR SPATPIVLVK QGHEPPTFIG WFFTWDPYKW TSHPSHKEVV
     DGSPAAASTI SEITAEVNNL RLSRWPGNGR AGAVALQALK GSQDSSENDL VRSPKSAGSR
     TSSSVSSTSA TINGGLRREQ LMHQAVEDLP EGVDPARREF YLSDSDFQDI FGKSKEEFYS
     MATWRQRQEK KQLGFF
//