ID PLST_HUMAN Reviewed; 630 AA. AC P13797; A8K579; B1AQ09; B4DGB4; B7Z6M1; Q86YI6; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 14-APR-2009, sequence version 4. DT 24-JUL-2024, entry version 239. DE RecName: Full=Plastin-3; DE AltName: Full=T-fimbrin {ECO:0000303|PubMed:9302997}; DE AltName: Full=T-plastin; GN Name=PLS3; 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 PARTIAL PROTEIN SEQUENCE. RX PubMed=3211125; DOI=10.1128/mcb.8.11.4659-4668.1988; RA Lin C.-S., Aebersold R.H., Kent S.B., Varma M., Leavitt J.; RT "Molecular cloning and characterization of plastin, a human leukocyte RT protein expressed in transformed human fibroblasts."; RL Mol. Cell. Biol. 8:4659-4668(1988). RN [2] RP SEQUENCE REVISION. RX PubMed=2378651; DOI=10.1128/mcb.10.4.1818-1821.1990; RA Lin C.-S., Aebersold R.H., Leavitt J.; RT "Correction of the N-terminal sequences of the human plastin isoforms by RT using anchored polymerase chain reaction: identification of a potential RT calcium-binding domain."; RL Mol. Cell. Biol. 10:1818-1821(1990). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Amygdala; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta, and Skin; 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 588-630. RX PubMed=8428952; DOI=10.1016/s0021-9258(18)53842-4; RA Lin C.-S., Park T., Chen Z.P., Leavitt J.; RT "Human plastin genes. Comparative gene structure, chromosome location, and RT differential expression in normal and neoplastic cells."; RL J. Biol. Chem. 268:2781-2792(1993). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326 AND THR-391, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293; SER-326 AND THR-391, AND RP 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 [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293 AND SER-326, AND RP IDENTIFICATION BY MASS 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 [12] RP INVOLVEMENT IN OSTEOP, POLYMORPHISM, AND VARIANTS OSTEOP ASN-253 INS AND RP 491-GLN--VAL-630 DEL. RX PubMed=24088043; DOI=10.1056/nejmoa1308223; RA van Dijk F.S., Zillikens M.C., Micha D., Riessland M., Marcelis C.L., RA de Die-Smulders C.E., Milbradt J., Franken A.A., Harsevoort A.J., RA Lichtenbelt K.D., Pruijs H.E., Rubio-Gozalbo M.E., Zwertbroek R., RA Moutaouakil Y., Egthuijsen J., Hammerschmidt M., Bijman R., Semeins C.M., RA Bakker A.D., Everts V., Klein-Nulend J., Campos-Obando N., Hofman A., RA te Meerman G.J., Verkerk A.J., Uitterlinden A.G., Maugeri A., RA Sistermans E.A., Waisfisz Q., Meijers-Heijboer H., Wirth B., Simon M.E., RA Pals G.; RT "PLS3 mutations in X-linked osteoporosis with fractures."; RL N. Engl. J. Med. 369:1529-1536(2013). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, 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 [14] {ECO:0007744|PDB:1AOA} RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 101-375. RX PubMed=9302997; DOI=10.1038/nsb0997-708; RA Goldsmith S.C., Pokala N., Shen W., Fedorov A.A., Matsudaira P., Almo S.C.; RT "The structure of an actin-crosslinking domain from human fimbrin."; RL Nat. Struct. Biol. 4:708-712(1997). RN [15] RP STRUCTURE BY NMR OF 520-630. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the fourth CH domain from human plastin 3 T- RT isoform."; RL Submitted (NOV-2004) to the PDB data bank. RN [16] RP VARIANT [LARGE SCALE ANALYSIS] ALA-488. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [17] RP INVOLVEMENT IN CHILDHOOD-ONSET PRIMARY OSTEOPOROSIS, AND VARIANT PRO-478. RX PubMed=24616189; DOI=10.1002/jbmr.2208; RA Fahiminiya S., Majewski J., Al-Jallad H., Moffatt P., Mort J., RA Glorieux F.H., Roschger P., Klaushofer K., Rauch F.; RT "Osteoporosis caused by mutations in PLS3: clinical and bone tissue RT characteristics."; RL J. Bone Miner. Res. 29:1805-1814(2014). RN [18] RP INVOLVEMENT IN CHILDHOOD-ONSET PRIMARY OSTEOPOROSIS, AND VARIANTS RP 256-ARG--VAL-630 DEL AND SER-446. RX PubMed=28748388; DOI=10.1007/s00198-017-4150-9; RA Kaempe A.J., Costantini A., Maekitie R.E., Jaentti N., Valta H., RA Maeyraenpaeae M., Kroeger H., Pekkinen M., Taylan F., Jiao H., Maekitie O.; RT "PLS3 sequencing in childhood-onset primary osteoporosis identifies two RT novel disease-causing variants."; RL Osteoporos. Int. 28:3023-3032(2017). RN [19] RP INVOLVEMENT IN X-LINKED OSTEOGENESIS IMPERFECTA. RX PubMed=33166085; DOI=10.1002/mgg3.1525; RA Hu J., Li L.J., Zheng W.B., Zhao D.C., Wang O., Jiang Y., Xing X.P., Li M., RA Xia W.; RT "A novel mutation in PLS3 causes extremely rare X-linked osteogenesis RT imperfecta."; RL Mol. Genet. Genomic Med. 8:e1525-e1525(2020). RN [20] RP INVOLVEMENT IN X-LINKED OSTEOGENESIS IMPERFECTA, AND VARIANT ARG-229. RX PubMed=34946798; DOI=10.3390/genes12121851; RA Brlek P., Anticevic D., Molnar V., Matisic V., Robinson K., Aradhya S., RA Krpan D., Primorac D.; RT "X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in RT PLS3."; RL Genes (Basel) 12:0-0(2021). RN [21] RP INVOLVEMENT IN DIH5, AND VARIANTS DIH5 PHE-120; VAL-206; VAL-235; LYS-270; RP LEU-352; GLU-364; CYS-499 AND VAL-592. RX PubMed=37751738; DOI=10.1016/j.ajhg.2023.09.002; RA Petit F., Longoni M., Wells J., Maser R.S., Bogenschutz E.L., Dysart M.J., RA Contreras H.T.M., Frenois F., Pober B.R., Clark R.D., Giampietro P.F., RA Ropers H.H., Hu H., Loscertales M., Wagner R., Ai X., Brand H., RA Jourdain A.S., Delrue M.A., Gilbert-Dussardier B., Devisme L., Keren B., RA McCulley D.J., Qiao L., Hernan R., Wynn J., Scott T.M., Calame D.G., RA Coban-Akdemir Z., Hernandez P., Hernandez-Garcia A., Yonath H., RA Lupski J.R., Shen Y., Chung W.K., Scott D.A., Bult C.J., Donahoe P.K., RA High F.A.; RT "PLS3 missense variants affecting the actin-binding domains cause X-linked RT congenital diaphragmatic hernia and body-wall defects."; RL Am. J. Hum. Genet. 110:1787-1803(2023). CC -!- FUNCTION: Actin-bundling protein. CC -!- SUBUNIT: Monomer. CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P13797-1; Sequence=Displayed; CC Name=2; CC IsoId=P13797-2; Sequence=VSP_056236, VSP_056237; CC Name=3; CC IsoId=P13797-3; Sequence=VSP_056235; CC -!- TISSUE SPECIFICITY: Expressed in a variety of organs, including muscle, CC brain, uterus and esophagus. CC -!- POLYMORPHISM: Genetic variations in PLS3 define the bone mineral CC density quantitative trait locus 18 (BMND18) [MIM:300910]. Variance in CC bone mineral density influences bone mass, contributes to size CC determination in the general population, and is a susceptibility factor CC for osteoporotic fractures. {ECO:0000269|PubMed:24088043}. CC -!- DISEASE: Osteoporosis (OSTEOP) [MIM:166710]: A systemic skeletal CC disorder characterized by decreased bone mass and deterioration of bone CC microarchitecture without alteration in the composition of bone. The CC result is fragile bones and an increased risk of fractures, even after CC minimal trauma. Osteoporosis is a chronic condition of multifactorial CC etiology and is usually clinically silent until a fracture occurs. CC {ECO:0000269|PubMed:24088043}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC It has been proposed that loss-of-function variants may be associated CC with X-linked osteoporosis, while missense variants affecting the CC actin-binding domains might have a gain-of-function effect and may CC cause X-linked diaphragmatic hernia. {ECO:0000303|PubMed:37751738}. CC -!- DISEASE: Note=Variants in PLS3 have been suggested to be associated CC with a variety of abnormalities of the skeletal system, ranging from CC non-syndromic childhood-onset osteoporosis to osteogenesis imperfecta. CC {ECO:0000269|PubMed:24616189, ECO:0000269|PubMed:28748388, CC ECO:0000269|PubMed:33166085, ECO:0000269|PubMed:34946798}. CC -!- DISEASE: Diaphragmatic hernia 5, X-linked (DIH5) [MIM:306950]: A form CC of congenital diaphragmatic hernia, a posterolateral defect of the CC diaphragm, generally located on the left side, that permits the CC herniation of abdominal viscera into the thorax. The lungs are CC hypoplastic and have abnormal vessels that cause respiratory CC insufficiency and persistent pulmonary hypertension with high CC mortality. About one third of cases have cardiovascular malformations CC and lesser proportions have skeletal, neural, genitourinary, CC gastrointestinal or other defects. DIH5 is usually transmitted in an X- CC linked recessive pattern with males being severely affected. Early CC death is frequent. Note=The disease is caused by variants affecting the CC gene represented in this entry. It has been proposed that loss-of- CC function variants may be associated with X-linked osteoporosis, while CC missense variants affecting the actin-binding domains might have a CC gain-of-function effect and may cause X-linked diaphragmatic hernia. CC {ECO:0000303|PubMed:37751738}. 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; M22299; AAB02844.1; -; mRNA. DR EMBL; M34427; AAA36759.1; -; mRNA. DR EMBL; AK291194; BAF83883.1; -; mRNA. DR EMBL; AK294509; BAG57725.1; -; mRNA. DR EMBL; AK300575; BAH13307.1; -; mRNA. DR EMBL; AK312391; BAG35308.1; -; mRNA. DR EMBL; AC003983; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005000; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL589842; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471120; EAX02614.1; -; Genomic_DNA. DR EMBL; BC039049; AAH39049.1; -; mRNA. DR EMBL; BC056898; AAH56898.1; -; mRNA. DR EMBL; L05491; AAA61214.1; -; Genomic_DNA. DR CCDS; CCDS14568.1; -. [P13797-1] DR CCDS; CCDS78499.1; -. [P13797-2] DR PIR; A34789; A34789. DR RefSeq; NP_001129497.1; NM_001136025.4. [P13797-1] DR RefSeq; NP_001165806.1; NM_001172335.2. DR RefSeq; NP_001269266.1; NM_001282337.1. [P13797-2] DR RefSeq; NP_001269267.1; NM_001282338.1. [P13797-3] DR RefSeq; NP_005023.2; NM_005032.6. [P13797-1] DR RefSeq; XP_011535836.1; XM_011537534.1. DR PDB; 1AOA; X-ray; 2.40 A; A=101-375. DR PDB; 1WJO; NMR; -; A=520-630. DR PDB; 7R94; EM; 2.60 A; F/G/H=1-630. DR PDB; 7SX8; EM; 9.00 A; D=1-630. DR PDB; 7SX9; EM; 10.00 A; D=1-630. DR PDB; 7SXA; EM; 6.87 A; A=1-630. DR PDBsum; 1AOA; -. DR PDBsum; 1WJO; -. DR PDBsum; 7R94; -. DR PDBsum; 7SX8; -. DR PDBsum; 7SX9; -. DR PDBsum; 7SXA; -. DR AlphaFoldDB; P13797; -. DR BMRB; P13797; -. DR EMDB; EMD-24323; -. DR EMDB; EMD-25371; -. DR EMDB; EMD-25494; -. DR EMDB; EMD-25495; -. DR EMDB; EMD-25496; -. DR SMR; P13797; -. DR BioGRID; 111372; 240. DR IntAct; P13797; 42. DR MINT; P13797; -. DR STRING; 9606.ENSP00000348163; -. DR GlyGen; P13797; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P13797; -. DR MetOSite; P13797; -. DR PhosphoSitePlus; P13797; -. DR SwissPalm; P13797; -. DR BioMuta; PLS3; -. DR DMDM; 226694201; -. DR jPOST; P13797; -. DR MassIVE; P13797; -. DR PaxDb; 9606-ENSP00000348163; -. DR PeptideAtlas; P13797; -. DR PRIDE; P13797; -. DR ProteomicsDB; 4120; -. DR ProteomicsDB; 52987; -. [P13797-1] DR ProteomicsDB; 6788; -. DR Pumba; P13797; -. DR Antibodypedia; 44530; 253 antibodies from 26 providers. DR DNASU; 5358; -. DR Ensembl; ENST00000289290.7; ENSP00000289290.4; ENSG00000102024.19. [P13797-2] DR Ensembl; ENST00000355899.8; ENSP00000348163.3; ENSG00000102024.19. [P13797-1] DR Ensembl; ENST00000539310.5; ENSP00000445339.2; ENSG00000102024.19. [P13797-1] DR GeneID; 5358; -. DR KEGG; hsa:5358; -. DR MANE-Select; ENST00000355899.8; ENSP00000348163.3; NM_005032.7; NP_005023.2. DR UCSC; uc004eqd.4; human. [P13797-1] DR AGR; HGNC:9091; -. DR CTD; 5358; -. DR DisGeNET; 5358; -. DR GeneCards; PLS3; -. DR HGNC; HGNC:9091; PLS3. DR HPA; ENSG00000102024; Low tissue specificity. DR MalaCards; PLS3; -. DR MIM; 166710; phenotype. DR MIM; 300131; gene. DR MIM; 300910; phenotype. DR MIM; 306950; phenotype. DR neXtProt; NX_P13797; -. DR OpenTargets; ENSG00000102024; -. DR Orphanet; 391330; X-linked osteoporosis with fractures. DR PharmGKB; PA33418; -. DR VEuPathDB; HostDB:ENSG00000102024; -. DR eggNOG; KOG0046; Eukaryota. DR GeneTree; ENSGT00950000183097; -. DR InParanoid; P13797; -. DR OMA; TVNHLYV; -. DR OrthoDB; 5475188at2759; -. DR PhylomeDB; P13797; -. DR TreeFam; TF300680; -. DR PathwayCommons; P13797; -. DR SignaLink; P13797; -. DR BioGRID-ORCS; 5358; 24 hits in 773 CRISPR screens. DR ChiTaRS; PLS3; human. DR EvolutionaryTrace; P13797; -. DR GeneWiki; PLS3; -. DR GenomeRNAi; 5358; -. DR Pharos; P13797; Tbio. DR PRO; PR:P13797; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P13797; Protein. DR Bgee; ENSG00000102024; Expressed in blood vessel layer and 210 other cell types or tissues. DR ExpressionAtlas; P13797; baseline and differential. DR GO; GO:0005884; C:actin filament; IBA:GO_Central. DR GO; GO:0032432; C:actin filament bundle; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0051017; P:actin filament bundle assembly; IBA:GO_Central. DR GO; GO:0051639; P:actin filament network formation; IBA:GO_Central. DR GO; GO:0060348; P:bone development; IMP:UniProtKB. DR CDD; cd21328; CH_PLS3_rpt2; 1. DR CDD; cd21331; CH_PLS3_rpt3; 1. DR CDD; cd21334; CH_PLS3_rpt4; 1. DR CDD; cd21292; CH_PLS_rpt1; 1. DR CDD; cd00051; EFh; 1. DR DisProt; DP02682; -. DR Gene3D; 1.10.418.10; Calponin-like domain; 4. DR Gene3D; 1.10.238.10; EF-hand; 1. DR InterPro; IPR001589; Actinin_actin-bd_CS. DR InterPro; IPR001715; CH_dom. DR InterPro; IPR036872; CH_dom_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR039959; Fimbrin/Plastin. DR PANTHER; PTHR19961; FIMBRIN/PLASTIN; 1. DR PANTHER; PTHR19961:SF32; PLASTIN-3; 1. DR Pfam; PF00307; CH; 4. DR Pfam; PF13499; EF-hand_7; 1. DR SMART; SM00033; CH; 4. DR SMART; SM00054; EFh; 2. DR SUPFAM; SSF47576; Calponin-homology domain, CH-domain; 1. DR SUPFAM; SSF47473; EF-hand; 1. DR PROSITE; PS00019; ACTININ_1; 2. DR PROSITE; PS00020; ACTININ_2; 2. DR PROSITE; PS50021; CH; 4. DR PROSITE; PS00018; EF_HAND_1; 2. DR PROSITE; PS50222; EF_HAND_2; 2. PE 1: Evidence at protein level; KW 3D-structure; Actin-binding; Alternative splicing; Calcium; Cytoplasm; KW Direct protein sequencing; Disease variant; Metal-binding; Osteoporosis; KW Phosphoprotein; Reference proteome; Repeat. FT CHAIN 1..630 FT /note="Plastin-3" FT /id="PRO_0000073747" FT DOMAIN 12..47 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 52..87 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 123..239 FT /note="Calponin-homology (CH) 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT DOMAIN 267..378 FT /note="Calponin-homology (CH) 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT DOMAIN 397..506 FT /note="Calponin-homology (CH) 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT DOMAIN 518..627 FT /note="Calponin-homology (CH) 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT REGION 109..382 FT /note="Actin-binding 1" FT REGION 383..627 FT /note="Actin-binding 2" FT BINDING 25 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 27 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 29 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 36 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 65 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 67 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 69 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 71 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 76 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT MOD_RES 268 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99K51" FT MOD_RES 293 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 326 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 339 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 391 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT VAR_SEQ 1..45 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_056235" FT VAR_SEQ 1..24 FT /note="MDEMATTQISKDELDELKEAFAKV -> ME (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056236" FT VAR_SEQ 296 FT /note="I -> IKLIDFSNSV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056237" FT VARIANT 120 FT /note="S -> F (in DIH5; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37751738" FT /id="VAR_089124" FT VARIANT 206 FT /note="A -> V (in DIH5; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:37751738" FT /id="VAR_089125" FT VARIANT 229 FT /note="G -> R (found in a patient with X-linked FT osteogenesis imperfecta; uncertain significance)" FT /evidence="ECO:0000269|PubMed:34946798" FT /id="VAR_089126" FT VARIANT 235 FT /note="I -> V (in DIH5; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37751738" FT /id="VAR_089127" FT VARIANT 253 FT /note="A -> AN (in OSTEOP; uncertain significance; no FT effect on protein level in patient's fibroblasts)" FT /evidence="ECO:0000269|PubMed:24088043" FT /id="VAR_070278" FT VARIANT 256..630 FT /note="Missing (found in a patient with childhood-onset FT primary osteoporosis; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:28748388" FT /id="VAR_089128" FT VARIANT 270 FT /note="E -> K (in DIH5; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:37751738" FT /id="VAR_089129" FT VARIANT 352 FT /note="F -> L (in DIH5; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37751738" FT /id="VAR_089130" FT VARIANT 364 FT /note="K -> E (in DIH5; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37751738" FT /id="VAR_089131" FT VARIANT 446 FT /note="N -> S (found in a patient with childhood-onset FT primary osteoporosis; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28748388" FT /id="VAR_089132" FT VARIANT 478 FT /note="L -> P (found in a patient with childhood-onset FT primary osteoporosis; uncertain significance)" FT /evidence="ECO:0000269|PubMed:24616189" FT /id="VAR_089133" FT VARIANT 488 FT /note="D -> A (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035462" FT VARIANT 491..630 FT /note="Missing (in OSTEOP; uncertain significance)" FT /evidence="ECO:0000269|PubMed:24088043" FT /id="VAR_089134" FT VARIANT 499 FT /note="W -> C (in DIH5; likely pathogenic; the orthologous FT mutation in mice results in death within the first 2 days FT after birth; the animals display several phenotypes at late FT gestation and neonatal time points, including diaphragm FT abnormalities and anterior body-wall defects)" FT /evidence="ECO:0000269|PubMed:37751738" FT /id="VAR_089135" FT VARIANT 592 FT /note="M -> V (in DIH5; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37751738" FT /id="VAR_089136" FT HELIX 123..136 FT /evidence="ECO:0007829|PDB:1AOA" FT TURN 137..139 FT /evidence="ECO:0007829|PDB:1AOA" FT TURN 144..146 FT /evidence="ECO:0007829|PDB:1AOA" FT TURN 151..154 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 155..159 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 160..162 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 164..173 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 180..182 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 190..206 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 216..220 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 224..244 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 261..265 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 269..283 FT /evidence="ECO:0007829|PDB:1AOA" FT TURN 294..298 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 300..309 FT /evidence="ECO:0007829|PDB:1AOA" FT STRAND 315..317 FT /evidence="ECO:0007829|PDB:1AOA" FT TURN 326..329 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 333..344 FT /evidence="ECO:0007829|PDB:1AOA" FT TURN 345..348 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 355..359 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 363..374 FT /evidence="ECO:0007829|PDB:1AOA" FT HELIX 398..409 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 419..422 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 427..435 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 442..444 FT /evidence="ECO:0007829|PDB:7R94" FT STRAND 452..454 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 455..471 FT /evidence="ECO:0007829|PDB:7R94" FT TURN 472..474 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 483..487 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 491..512 FT /evidence="ECO:0007829|PDB:7R94" FT STRAND 513..517 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 525..531 FT /evidence="ECO:0007829|PDB:7R94" FT TURN 532..535 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 547..549 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 553..562 FT /evidence="ECO:0007829|PDB:7R94" FT TURN 569..571 FT /evidence="ECO:0007829|PDB:1WJO" FT TURN 579..581 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 582..596 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 605..608 FT /evidence="ECO:0007829|PDB:7R94" FT HELIX 612..626 FT /evidence="ECO:0007829|PDB:7R94" SQ SEQUENCE 630 AA; 70811 MW; 631E6F803DC56A56 CRC64; MDEMATTQIS KDELDELKEA FAKVDLNSNG FICDYELHEL FKEANMPLPG YKVREIIQKL MLDGDRNKDG KISFDEFVYI FQEVKSSDIA KTFRKAINRK EGICALGGTS ELSSEGTQHS YSEEEKYAFV NWINKALEND PDCRHVIPMN PNTDDLFKAV GDGIVLCKMI NLSVPDTIDE RAINKKKLTP FIIQENLNLA LNSASAIGCH VVNIGAEDLR AGKPHLVLGL LWQIIKIGLF ADIELSRNEA LAALLRDGET LEELMKLSPE ELLLRWANFH LENSGWQKIN NFSADIKDSK AYFHLLNQIA PKGQKEGEPR IDINMSGFNE TDDLKRAESM LQQADKLGCR QFVTPADVVS GNPKLNLAFV ANLFNKYPAL TKPENQDIDW TLLEGETREE RTFRNWMNSL GVNPHVNHLY ADLQDALVIL QLYERIKVPV DWSKVNKPPY PKLGANMKKL ENCNYAVELG KHPAKFSLVG IGGQDLNDGN QTLTLALVWQ LMRRYTLNVL EDLGDGQKAN DDIIVNWVNR TLSEAGKSTS IQSFKDKTIS SSLAVVDLID AIQPGCINYD LVKSGNLTED DKHNNAKYAV SMARRIGARV YALPEDLVEV KPKMVMTVFA CLMGRGMKRV //