ID AVIL_HUMAN Reviewed; 819 AA. AC O75366; B2RAU7; Q2NKM9; DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 02-SEP-2026, entry version 191. DE RecName: Full=Advillin {ECO:0000305}; DE AltName: Full=p92; GN Name=AVIL {ECO:0000312|HGNC:HGNC:14188}; 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 VARIANT GLU-204. RC TISSUE=Uterus; RX PubMed=9664034; DOI=10.1242/jcs.111.15.2129; RA Marks P.W., Arai M., Bandura J.L., Kwiatkowski D.J.; RT "Advillin (p92): a new member of the gelsolin/villin family of actin RT regulatory proteins."; RL J. Cell Sci. 111:2129-2136(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-204. RC TISSUE=Brain; 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], AND VARIANT GLU-204. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLU-204. 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 TISSUE SPECIFICITY. RX PubMed=12034507; DOI=10.1016/s0378-1119(02)00478-x; RA Tumer Z., Croucher P.J., Jensen L.R., Hampe J., Hansen C., Kalscheuer V., RA Ropers H.H., Tommerup N., Schreiber S.; RT "Genomic structure, chromosome mapping and expression analysis of the human RT AVIL gene, and its exclusion as a candidate for locus for inflammatory RT bowel disease at 12q13-14 (IBD2)."; RL Gene 288:179-185(2002). RN [7] RP FUNCTION. RX PubMed=20393563; DOI=10.1038/nature08895; RA Kim J., Lee J.E., Heynen-Genel S., Suyama E., Ono K., Lee K., Ideker T., RA Aza-Blanc P., Gleeson J.G.; RT "Functional genomic screen for modulators of ciliogenesis and cilium RT length."; RL Nature 464:1048-1051(2010). RN [8] RP STRUCTURE BY NMR OF 784-819, INTERACTION WITH F-ACTIN, AND MUTAGENESIS OF RP TRP-62. 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 [9] RP INVOLVEMENT IN NPHS21, VARIANTS NPHS21 GLN-135; MET-425 AND HIS-446, RP CHARACTERIZATION OF VARIANTS NPHS21 GLN-135 AND MET-425, FUNCTION, RP INTERACTION WITH F-ACTIN, INTERACTION WITH PLCE1 AND ARP2/3 COMPLEX, TISSUE RP SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=29058690; DOI=10.1172/jci94138; RA Rao J., Ashraf S., Tan W., van der Ven A.T., Gee H.Y., Braun D.A., RA Feher K., George S.P., Esmaeilniakooshkghazi A., Choi W.I., RA Jobst-Schwan T., Schneider R., Schmidt J.M., Widmeier E., Warejko J.K., RA Hermle T., Schapiro D., Lovric S., Shril S., Daga A., Nayir A., Shenoy M., RA Tse Y., Bald M., Helmchen U., Mir S., Berdeli A., Kari J.A., El Desoky S., RA Soliman N.A., Bagga A., Mane S., Jairajpuri M.A., Lifton R.P., Khurana S., RA Martins J.C., Hildebrandt F.; RT "Advillin acts upstream of phospholipase C 1 in steroid-resistant nephrotic RT syndrome."; RL J. Clin. Invest. 127:4257-4269(2017). CC -!- FUNCTION: Ca(2+)-regulated actin-binding protein which plays an CC important role in actin bundling (PubMed:29058690). May have a unique CC function in the morphogenesis of neuronal cells which form ganglia. CC Required for SREC1-mediated regulation of neurite-like outgrowth. Plays CC a role in regenerative sensory axon outgrowth and remodeling processes CC after peripheral injury in neonates. Involved in the formation of long CC fine actin-containing filopodia-like structures in fibroblast. Plays a CC role in ciliogenesis. In podocytes, controls lamellipodia formation CC through the regulation of EGF-induced diacylglycerol generation by CC PLCE1 and ARP2/3 complex assembly (PubMed:29058690). CC {ECO:0000269|PubMed:20393563, ECO:0000269|PubMed:29058690}. CC -!- SUBUNIT: Associates (via C-terminus) with F-actin (PubMed:15096633, CC PubMed:29058690). Interacts with SCARF1 (By similarity). Interacts with CC PLCE1 (PubMed:29058690). Interacts with ACTR2 and ACTR3; associates CC with the ARP2/3 complex (PubMed:29058690). CC {ECO:0000250|UniProtKB:O88398, ECO:0000269|PubMed:15096633, CC ECO:0000269|PubMed:29058690}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:29058690}. Cell projection, lamellipodium CC {ECO:0000269|PubMed:29058690}. Cell junction, focal adhesion CC {ECO:0000269|PubMed:29058690}. Cell projection, neuron projection CC {ECO:0000250|UniProtKB:Q9WU06}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q9WU06}. Note=In podocytes, present in the F- CC actin-enriched cell periphery that generates lamellipodia and focal CC adhesions. {ECO:0000269|PubMed:29058690}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75366-1; Sequence=Displayed; CC Name=2; CC IsoId=O75366-2; Sequence=VSP_036961; CC -!- TISSUE SPECIFICITY: Most highly expressed in the small intestine and CC colonic lining. Weaker expression also detected in the thymus, CC prostate, testes and uterus (PubMed:12034507). Expressed in podocytes CC (at protein level) (PubMed:29058690). {ECO:0000269|PubMed:12034507, CC ECO:0000269|PubMed:29058690}. CC -!- DISEASE: Nephrotic syndrome 21 (NPHS21) [MIM:618594]: A form of CC nephrotic syndrome, a renal disease clinically characterized by severe CC proteinuria, resulting in complications such as hypoalbuminemia, CC hyperlipidemia and edema. Kidney biopsies show non-specific histologic CC changes such as focal segmental glomerulosclerosis and diffuse CC mesangial proliferation. Some affected individuals have an inherited CC steroid-resistant form that progresses to end-stage renal failure. CC NPHS21 is an autosomal recessive, rapidly progressive, steroid- CC resistant form characterized by onset of kidney dysfunction in the CC first year of life. Some patients may have variable extra-renal CC manifestations. {ECO:0000269|PubMed:29058690}. Note=The disease is CC caused by variants affecting the gene represented in this 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; AF041449; AAC25051.1; -; mRNA. DR EMBL; AK314362; BAG36994.1; -; mRNA. DR EMBL; AC025165; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW97080.1; -; Genomic_DNA. DR EMBL; BC111730; AAI11731.1; -; mRNA. DR CCDS; CCDS8959.1; -. [O75366-1] DR RefSeq; NP_006567.3; NM_006576.4. [O75366-1] DR RefSeq; XP_047284070.1; XM_047428114.1. [O75366-1] DR PDB; 1UND; NMR; -; A=784-819. DR AlphaFoldDB; O75366; -. DR BMRB; O75366; -. DR SMR; O75366; -. DR BioGRID; 115918; 33. DR FunCoup; O75366; 152. DR IntAct; O75366; 35. DR STRING; 9606.ENSP00000257861; -. DR GuidetoPHARMACOLOGY; 3340; -. DR iPTMnet; O75366; -. DR PhosphoSitePlus; O75366; -. DR BioMuta; AVIL; -. DR jPOST; O75366; -. DR MassIVE; O75366; -. DR PaxDb; 9606-ENSP00000257861; -. DR PeptideAtlas; O75366; -. DR ProteomicsDB; 49932; -. [O75366-1] DR ProteomicsDB; 49933; -. [O75366-2] DR Antibodypedia; 28969; 142 antibodies from 22 providers. DR DNASU; 10677; -. DR Ensembl; ENST00000257861.7; ENSP00000257861.3; ENSG00000135407.11. [O75366-1] DR Ensembl; ENST00000549994.2; ENSP00000449239.2; ENSG00000135407.11. [O75366-1] DR GeneID; 10677; -. DR KEGG; hsa:10677; -. DR MANE-Select; ENST00000549994.2; ENSP00000449239.2; NM_006576.4; NP_006567.3. DR UCSC; uc001sqj.4; human. [O75366-1] DR AGR; HGNC:14188; -. DR ClinPGx; PA38380; -. DR CTD; 10677; -. DR DisGeNET; 10677; -. DR GeneCards; AVIL; -. DR HGNC; HGNC:14188; AVIL. DR HPA; ENSG00000135407; Low tissue specificity. DR MalaCards; AVIL; -. DR MIM; 613397; gene. DR MIM; 618594; phenotype. DR OpenTargets; ENSG00000135407; -. DR Orphanet; 656; Hereditary steroid-resistant nephrotic syndrome. DR VEuPathDB; HostDB:ENSG00000135407; -. DR eggNOG; KOG0443; Eukaryota. DR GeneTree; ENSGT00940000159587; -. DR HOGENOM; CLU_002568_3_1_1; -. DR InParanoid; O75366; -. DR OMA; DPNIWSA; -. DR OrthoDB; 6375767at2759; -. DR PAN-GO; O75366; 6 GO annotations based on evolutionary models. DR PhylomeDB; O75366; -. DR PathwayCommons; O75366; -. DR SignaLink; O75366; -. DR Agora; ENSG00000135407; -. DR BioGRID-ORCS; 10677; 26 hits in 1147 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; AVIL; human. DR EvolutionaryTrace; O75366; -. DR GenomeRNAi; 10677; -. DR Pharos; O75366; Tbio. DR PRO; PR:O75366; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; O75366; protein. DR Bgee; ENSG00000135407; Expressed in dorsal root ganglion and 141 other cell types or tissues. DR ExpressionAtlas; O75366; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc. DR GO; GO:0005884; C:actin filament; IDA:UniProtKB. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0042995; C:cell projection; ISS:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB. DR GO; GO:0003779; F:actin binding; ISS:UniProtKB. DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB. DR GO; GO:0071933; F:Arp2/3 complex binding; IDA:UniProtKB. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IBA:GO_Central. DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB. 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:0060271; P:cilium assembly; IMP:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:UniProtKB. DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB. DR GO; GO:1900480; P:regulation of diacylglycerol biosynthetic process; IMP:UniProtKB. 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 FunFam; 3.40.20.10:FF:000001; Gelsolin; 1. DR FunFam; 3.40.20.10:FF:000002; Gelsolin; 1. DR FunFam; 3.40.20.10:FF:000004; Gelsolin; 1. DR FunFam; 3.40.20.10:FF:000005; Gelsolin; 1. DR FunFam; 3.40.20.10:FF:000027; Villin 1; 1. DR FunFam; 1.10.950.10:FF:000005; Villin-1; 1. DR FunFam; 3.40.20.10:FF:000035; Villin-1; 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:SF33; ADVILLIN; 1. DR PANTHER; PTHR11977; VILLIN; 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. PE 1: Evidence at protein level; KW 3D-structure; Actin capping; Actin-binding; Alternative splicing; Calcium; KW Cell junction; Cell projection; Cytoplasm; Cytoskeleton; Disease variant; KW Phosphoprotein; Proteomics identification; Reference proteome; Repeat. FT CHAIN 1..819 FT /note="Advillin" FT /id="PRO_0000218736" FT REPEAT 24..73 FT /note="Gelsolin-like 1" FT REPEAT 145..185 FT /note="Gelsolin-like 2" FT REPEAT 262..306 FT /note="Gelsolin-like 3" FT REPEAT 403..454 FT /note="Gelsolin-like 4" FT REPEAT 525..565 FT /note="Gelsolin-like 5" FT REPEAT 628..669 FT /note="Gelsolin-like 6" FT DOMAIN 753..819 FT /note="HP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00595" FT REGION 1..731 FT /note="Core" FT /evidence="ECO:0000250" FT REGION 628..819 FT /note="Required for interaction with F-actin" FT /evidence="ECO:0000269|PubMed:29058690" FT REGION 731..819 FT /note="Headpiece" FT /evidence="ECO:0000250" FT BINDING 109..116 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- FT inositol-4,5-bisphosphate)" FT /ligand_id="ChEBI:CHEBI:58456" FT /evidence="ECO:0000250" FT BINDING 135..143 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- FT inositol-4,5-bisphosphate)" FT /ligand_id="ChEBI:CHEBI:58456" FT /evidence="ECO:0000250" FT MOD_RES 85 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:O88398" FT MOD_RES 758 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:O88398" FT VAR_SEQ 1..21 FT /note="MPLTSAFRAVDNDPGIIVWRI -> MSSTGHPGSYKIWG (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_036961" FT VARIANT 135 FT /note="R -> Q (in NPHS21; inhibited actin bundling FT capacity; slightly decreased interaction with PLCE1; FT disrupted EGF-induced diacylglycerol generation by PLCE1; FT dbSNP:rs138047529)" FT /evidence="ECO:0000269|PubMed:29058690" FT /id="VAR_083229" FT VARIANT 204 FT /note="K -> E (in dbSNP:rs2172521)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16541075, FT ECO:0000269|PubMed:9664034" FT /id="VAR_054974" FT VARIANT 425 FT /note="L -> M (in NPHS21; inhibited actin bundling FT capacity; decreases interaction with PLCE1; disrupted FT EGF-induced diacylglycerol generation by PLCE1; FT dbSNP:rs763782471)" FT /evidence="ECO:0000269|PubMed:29058690" FT /id="VAR_083230" FT VARIANT 446 FT /note="R -> H (in NPHS21; uncertain significance; FT dbSNP:rs1334894971)" FT /evidence="ECO:0000269|PubMed:29058690" FT /id="VAR_083231" FT MUTAGEN 62 FT /note="W->A: Reduces interaction with F-actin." FT /evidence="ECO:0000269|PubMed:15096633" FT CONFLICT 445 FT /note="G -> D (in Ref. 1; AAC25051)" FT /evidence="ECO:0000305" FT HELIX 787..794 FT /evidence="ECO:0007829|PDB:1UND" FT HELIX 798..803 FT /evidence="ECO:0007829|PDB:1UND" FT HELIX 806..817 FT /evidence="ECO:0007829|PDB:1UND" SQ SEQUENCE 819 AA; 92027 MW; F5EF3A94BA61E647 CRC64; MPLTSAFRAV DNDPGIIVWR IEKMELALVP VSAHGNFYEG DCYVILSTRR VASLLSQDIH FWIGKDSSQD EQSCAAIYTT QLDDYLGGSP VQHREVQYHE SDTFRGYFKQ GIIYKQGGVA SGMKHVETNT YDVKRLLHVK GKRNIRATEV EMSWDSFNRG DVFLLDLGKV IIQWNGPESN SGERLKAMLL AKDIRDRERG GRAKIGVIEG DKEAASPELM KVLQDTLGRR SIIKPTVPDE IIDQKQKSTI MLYHISDSAG QLAVTEVATR PLVQDLLNHD DCYILDQSGT KIYVWKGKGA TKAEKQAAMS KALGFIKMKS YPSSTNVETV NDGAESAMFK QLFQKWSVKD QTMGLGKTFS IGKIAKVFQD KFDVTLLHTK PEVAAQERMV DDGNGKVEVW RIENLELVPV EYQWYGFFYG GDCYLVLYTY EVNGKPHHIL YIWQGRHASQ DELAASAYQA VEVDRQFDGA AVQVRVRMGT EPRHFMAIFK GKLVIFEGGT SRKGNAEPDP PVRLFQIHGN DKSNTKAVEV PAFASSLNSN DVFLLRTQAE HYLWYGKGSS GDERAMAKEL ASLLCDGSEN TVAEGQEPAE FWDLLGGKTP YANDKRLQQE ILDVQSRLFE CSNKTGQFVV TEITDFTQDD LNPTDVMLLD TWDQVFLWIG AEANATEKES ALATAQQYLH THPSGRDPDT PILIIKQGFE PPIFTGWFLA WDPNIWSAGK TYEQLKEELG DAAAIMRITA DMKNATLSLN SNDSEPKYYP IAVLLKNQNQ ELPEDVNPAK KENYLSEQDF VSVFGITRGQ FAALPGWKQL QMKKEKGLF //