{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:32:31Z","timestamp":1790627551026,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,7,20]]},"abstract":"<jats:p>\n                    A human disorder caused by mutation in nonmuscle actin has not been reported. We report here a variant of nonmuscle actin in a female patient with recurrent infections, photosensitivity, and mental retardation. She also had abnormalities in neutrophil chemotaxis, superoxide production, and membrane potential response. Two-dimensional PAGE analysis of proteins from neutrophils and other cell types from this patient demonstrated a unique protein spot migrating at 42 kDa with pI shifted slightly to neutral relative to normal \u03b2- and \u03b3-actin. Digestion peptide mapping and Western blotting showed this spot to be an abnormal actin. A full-length cDNA library was constructed by using mRNA from patient\u2019s cells and cDNA encoding the mutant \u03b2-actin molecule was identified by an\n                    <jats:italic>in vitro<\/jats:italic>\n                    translation method. Sequencing of the clones demonstrated a G-1174 to A substitution, predicting a glutamic acid-364 to lysine substitution in \u03b2-actin and eliminating a\n                    <jats:italic>Hin<\/jats:italic>\n                    fI DNase restriction site found in normal \u03b2-actin sequence. By\n                    <jats:italic>Hin<\/jats:italic>\n                    fI digestion and by sequencing, the mutation in one allele of patient\u2019s genomic DNA was confirmed. Though no defect in cell-free polymerization of actin was detected, this defect lies in a domain important for binding to profilin and other actin-regulatory molecules. In fact, the mutant actin bound to profilin less efficiently than normal actin did. Heterozygous expression of mutant \u03b2-actin in neutrophils and other cells of this patient may act in a dominant\u2013negative fashion to adversely affect cellular activities dependent on the function of nonmuscle actin.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.15.8693","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"8693-8698","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":104,"title":["A heterozygous mutation of \u03b2-actin associated with neutrophil dysfunction and recurrent infection"],"prefix":"10.1073","volume":"96","author":[{"given":"Hiroyuki","family":"Nunoi","sequence":"first","affiliation":[{"name":"Institute of Medical Science, University of Tokyo, Minatoku, Tokyo 108-8639, Japan; Department of Pediatrics, Kumamoto University Medical School, Kumamoto 860-8556, Japan; Sagami Chemical Research Center, Sagamihara, Kanagawa 229-0012, Japan; and Host Defense in National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo, Minatoku, Tokyo 108-8639, Japan; Department of Pediatrics, Kumamoto University Medical School, Kumamoto 860-8556, Japan; Sagami Chemical Research Center, Sagamihara, Kanagawa 229-0012, Japan; and Host Defense in National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo, Minatoku, Tokyo 108-8639, Japan; Department of Pediatrics, Kumamoto University Medical School, Kumamoto 860-8556, Japan; Sagami Chemical Research Center, Sagamihara, Kanagawa 229-0012, Japan; and Host Defense in National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seishi","family":"Kato","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo, Minatoku, Tokyo 108-8639, Japan; Department of Pediatrics, Kumamoto University Medical School, Kumamoto 860-8556, Japan; Sagami Chemical Research Center, Sagamihara, Kanagawa 229-0012, Japan; and Host Defense in National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L.","family":"Malech","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo, Minatoku, Tokyo 108-8639, Japan; Department of Pediatrics, Kumamoto University Medical School, Kumamoto 860-8556, Japan; Sagami Chemical Research Center, Sagamihara, Kanagawa 229-0012, Japan; and Host Defense in National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo, Minatoku, Tokyo 108-8639, Japan; Department of Pediatrics, Kumamoto University Medical School, Kumamoto 860-8556, Japan; Sagami Chemical Research Center, Sagamihara, Kanagawa 229-0012, Japan; and Host Defense in National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Kanegasaki","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo, Minatoku, Tokyo 108-8639, Japan; Department of Pediatrics, Kumamoto University Medical School, Kumamoto 860-8556, Japan; Sagami Chemical Research Center, Sagamihara, Kanagawa 229-0012, Japan; and Host Defense in National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,7,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3170605"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00579-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00273589"},{"key":"e_1_3_3_4_2","first-page":"707","volume":"103","author":"Taniguchi S","year":"1988","unstructured":"S Taniguchi, J Sagara, T Kakunaga J Biol Chem 103, 707\u2013713 (1988).","journal-title":"J Biol Chem"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197411212912101"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113761"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V73.7.1973.1973"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365516809076979"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1382"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1955.tb45983.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(12)80056-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.1.329.bloodjournal861329"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109880"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)41496-8"},{"key":"e_1_3_3_15_2","first-page":"243","volume":"150","author":"Kato S","year":"1988","unstructured":"S Kato, S Sekine, S W Oh, N S Kim, Y Umezawa, N Abe, M Yokoyama-Kobayashi, T Aoki Gene 150, 243\u2013250 (1988).","journal-title":"Gene"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)33270-2"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.22.6516"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1159\/000205956"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45933-9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.18.6133"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/132.2.337"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.6.2127"},{"key":"e_1_3_3_23_2","first-page":"pp.1","volume-title":"Actin Structure, Protein Profile, Actin","author":"Sheterline P","year":"1994","unstructured":"P Sheterline, J Sparrow Actin Structure, Protein Profile, Actin, ed P Sheterline (Academic, London), pp. pp.1\u201362 (1994)."},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1992.tb17274.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.2.619"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/365810a0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2848319"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2848318"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124773"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00462.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)67684-2"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/12.3.1687"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.96.15.8693","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T16:39:15Z","timestamp":1649867955000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.96.15.8693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,7,20]]},"references-count":32,"journal-issue":{"issue":"15","published-print":{"date-parts":[[1999,7,20]]}},"alternative-id":["10.1073\/pnas.96.15.8693"],"URL":"https:\/\/doi.org\/10.1073\/pnas.96.15.8693","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,7,20]]},"assertion":[{"value":"1998-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-07-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}