ID LIMA1_HUMAN Reviewed; 759 AA. AC Q9UHB6; B2RB09; Q2TAN7; Q59FE8; Q9BVF2; Q9H8J1; Q9HBN5; Q9NX96; Q9NXC3; AC Q9NXU6; Q9P0H8; Q9UHB5; DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 210. DE RecName: Full=LIM domain and actin-binding protein 1; DE AltName: Full=Epithelial protein lost in neoplasm; GN Name=LIMA1 {ECO:0000312|HGNC:HGNC:24636}; GN Synonyms=EPLIN {ECO:0000303|PubMed:10618726}, SREBP3; ORFNames=PP624; 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] (ISOFORMS ALPHA AND BETA), AND SUBCELLULAR RP LOCATION. RC TISSUE=Cervix carcinoma; RX PubMed=10618726; DOI=10.1038/sj.onc.1203206; RA Maul R.S., Chang D.D.; RT "EPLIN, epithelial protein lost in neoplasm."; RL Oncogene 18:7838-7841(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Hypothalamus; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA). RC TISSUE=Uterus; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA; BETA AND 3). RC TISSUE=Colon, Hepatoma, and Placenta; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA). RC TISSUE=Brain, Cervix, Colon, and Placenta; 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 232-759. RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [9] RP SUBCELLULAR LOCATION. RX PubMed=11256614; DOI=10.1093/embo-reports/kvd058; RA Simpson J.C., Wellenreuther R., Poustka A., Pepperkok R., Wiemann S.; RT "Systematic subcellular localization of novel proteins identified by large- RT scale cDNA sequencing."; RL EMBO Rep. 1:287-292(2000). RN [10] RP ALTERNATIVE PROMOTER USAGE, AND INDUCTION. RX PubMed=10806352; DOI=10.1016/s0378-1119(00)00144-x; RA Chen S., Maul R.S., Kim H.R., Chang D.D.; RT "Characterization of the human EPLIN (Epithelial protein lost in neoplasm) RT gene reveals distinct promoters for the two EPLIN isoforms."; RL Gene 248:69-76(2000). RN [11] RP FUNCTION, AND ACTIN-BINDING REGION. RX PubMed=12566430; DOI=10.1083/jcb.200212057; RA Maul R.S., Song Y., Amann K.J., Gerbin S.C., Pollard T.D., Chang D.D.; RT "EPLIN regulates actin dynamics by cross-linking and stabilizing RT filaments."; RL J. Cell Biol. 160:399-407(2003). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-362; SER-490; SER-686 AND RP SER-692, AND 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-362 AND SER-490, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells RT and high confident phosphopeptide identification by cross-validation of RT MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-490, 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-490; SER-686 AND SER-692, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-225; TYR-229; RP SER-362; SER-374; SER-490; SER-604; SER-609; SER-617; SER-686; SER-692 AND RP SER-698, AND 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 [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-604; SER-617 AND SER-686, AND 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 [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-4; SER-132; SER-225; SER-263; SER-343; SER-362; SER-374; RP SER-490; SER-604; SER-686 AND SER-692, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-343 (ISOFORM 4), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT RP SER-183 (ISOFORM 5), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [20] 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-350; SER-362; RP SER-365; SER-369; SER-374; SER-490; SER-686; SER-698 AND SER-726, 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 [22] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORMS 5 AND ALPHA), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-15; SER-55; SER-132; RP SER-263; SER-362; SER-374; SER-490; SER-601; SER-604; SER-609; SER-617 AND RP SER-686, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; 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 [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225; SER-362; SER-365; RP SER-374 AND SER-490, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [25] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH PXN. RX PubMed=24694988; DOI=10.1038/ki.2014.85; RA Tsurumi H., Harita Y., Kurihara H., Kosako H., Hayashi K., Matsunaga A., RA Kajiho Y., Kanda S., Miura K., Sekine T., Oka A., Ishizuka K., Horita S., RA Hattori M., Hattori S., Igarashi T.; RT "Epithelial protein lost in neoplasm modulates platelet-derived growth RT factor-mediated adhesion and motility of mesangial cells."; RL Kidney Int. 86:548-557(2014). RN [26] RP VARIANT ILE-25, CHARACTERIZATION OF VARIANT ILE-25, INTERACTION WITH NPCL1, RP AND POLYMORPHISM. RX PubMed=29880681; DOI=10.1126/science.aao6575; RA Zhang Y.Y., Fu Z.Y., Wei J., Qi W., Baituola G., Luo J., Meng Y.J., RA Guo S.Y., Yin H., Jiang S.Y., Li Y.F., Miao H.H., Liu Y., Wang Y., Li B.L., RA Ma Y.T., Song B.L.; RT "A LIMA1 variant promotes low plasma LDL cholesterol and decreases RT intestinal cholesterol absorption."; RL Science 360:1087-1092(2018). RN [27] RP STRUCTURE BY NMR OF 381-460. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the LIM domain of epithelial protein lost in RT neoplasm."; RL Submitted (JUN-2006) to the PDB data bank. CC -!- FUNCTION: Actin-binding protein involved in actin cytoskeleton CC regulation and dynamics. Increases the number and size of actin stress CC fibers and inhibits membrane ruffling. Inhibits actin filament CC depolymerization. Bundles actin filaments, delays filament nucleation CC and reduces formation of branched filaments (PubMed:12566430). Plays a CC role in cholesterol homeostasis. Influences plasma cholesterol levels CC through regulation of intestinal cholesterol absorption. May act as a CC scaffold protein by regulating NPC1L1 transportation, an essential CC protein for cholesterol absorption, to the plasma membrane by CC recruiting MYO5B to NPC1L1, and thus facilitates cholesterol uptake (By CC similarity). {ECO:0000250|UniProtKB:Q9ERG0, CC ECO:0000269|PubMed:12566430}. CC -!- SUBUNIT: Interacts with NPCL1; bridges NPC1L1 with MYO5B CC (PubMed:29880681). Interacts with MYO5B; bridges NPC1L1 with MYO5B CC (PubMed:29880681). Interacts with PXN; this complex stabilizes actin CC dynamics (PubMed:24694988). Interacts with F-actin and G-actin CC (PubMed:12566430). {ECO:0000269|PubMed:12566430, CC ECO:0000269|PubMed:24694988, ECO:0000269|PubMed:29880681}. CC -!- INTERACTION: CC Q9UHB6; P12830: CDH1; NbExp=2; IntAct=EBI-351479, EBI-727477; CC Q9UHB6; P35221: CTNNA1; NbExp=2; IntAct=EBI-351479, EBI-701918; CC Q9UHB6; P53355: DAPK1; NbExp=2; IntAct=EBI-351479, EBI-358616; CC Q9UHB6; P63104: YWHAZ; NbExp=2; IntAct=EBI-351479, EBI-347088; CC Q9UHB6; O46385: SVIL; Xeno; NbExp=3; IntAct=EBI-351479, EBI-6995105; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell junction, focal adhesion CC {ECO:0000269|PubMed:10618726, ECO:0000269|PubMed:24694988}. Cytoplasm, CC cytoskeleton. Cytoplasm, cytoskeleton, stress fiber CC {ECO:0000269|PubMed:10618726}. Cell membrane CC {ECO:0000250|UniProtKB:Q9ERG0}. Note=Expressed in the brush border CC membrane of the small intestine and colocalizes with NPC1L1 and MYO5B CC (PubMed:29880681). Colocalizes with PXN at focal adhesions in mesangial CC cells (PubMed:24694988). Colocalizes with actin stress fibers in CC quiescent cells. PDGF stimulation induced disassembly of stress fibers CC and formation of peripheral and dorsal ruffles, where LIMA1 is CC relocalized (By similarity). {ECO:0000250|UniProtKB:Q9ERG0, CC ECO:0000269|PubMed:24694988, ECO:0000269|PubMed:29880681}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=5; CC Name=Beta; CC IsoId=Q9UHB6-1; Sequence=Displayed; CC Name=Alpha; CC IsoId=Q9UHB6-2; Sequence=VSP_003116; CC Name=3; CC IsoId=Q9UHB6-3; Sequence=VSP_003117; CC Name=4; CC IsoId=Q9UHB6-4; Sequence=VSP_040136; CC Name=5; CC IsoId=Q9UHB6-5; Sequence=VSP_003116, VSP_040136; CC -!- TISSUE SPECIFICITY: Highly expressed in placenta, kidney, pancreas, CC prostate, ovary, spleen and heart. Also detected in lung, liver, brain, CC skeletal muscle, thymus, testis and intestine. Not detected in CC leukocytes. Isoform Beta expressed generally at very low levels. CC Isoform Alpha abundant in epithelial cells from mammary gland, prostate CC and in normal oral keratinocytes. Low levels in aortic endothelial CC cells and dermal fibroblasts. Not detectable in myocardium. CC {ECO:0000269|PubMed:24694988}. CC -!- INDUCTION: Down-regulated in some cancer cell lines. Isoform Alpha is CC induced by serum. Isoform Beta is constitutively expressed. CC {ECO:0000269|PubMed:10806352}. CC -!- DOMAIN: Contains at least 2 actin-binding domains, one on each side of CC the LIM domain. Both domains bind actin monomers and filaments. The C- CC terminal domain binds filaments more efficiently than the N-terminus. CC {ECO:0000269|PubMed:12566430}. CC -!- PTM: Phosphorylation of the C-terminal region by MAPK1/MAPK3 reduces CC its association with F-actin and contributes to actin filament CC reorganization and enhances cell motility. CC {ECO:0000250|UniProtKB:Q9ERG0}. CC -!- POLYMORPHISM: Genetic variations in LIMA1 influence low density CC lipoprotein cholesterol (LDL-C) variability and contribute to the low CC density lipoprotein cholesterol level quantitative trait locus 8 CC (LDLCQ8) [MIM:618079]. {ECO:0000269|PubMed:29880681}. CC -!- MISCELLANEOUS: [Isoform Beta]: Produced by alternative promoter usage. CC -!- MISCELLANEOUS: [Isoform Alpha]: Produced by alternative promoter usage. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing of isoform CC Beta. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative splicing. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG17267.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAA91120.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAD92749.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AF198454; AAF23755.1; -; mRNA. DR EMBL; AF198455; AAF23756.1; -; mRNA. DR EMBL; AF157325; AAF67491.1; -; mRNA. DR EMBL; AL136911; CAB66845.1; -; mRNA. DR EMBL; AK000372; BAA91120.1; ALT_FRAME; mRNA. DR EMBL; AK000335; BAA91092.1; -; mRNA. DR EMBL; AK023649; BAB14625.1; -; mRNA. DR EMBL; AK000057; BAA90914.1; -; mRNA. DR EMBL; AK314447; BAG37056.1; -; mRNA. DR EMBL; AB209512; BAD92749.1; ALT_INIT; mRNA. DR EMBL; CH471111; EAW58135.1; -; Genomic_DNA. DR EMBL; BC001247; AAH01247.2; -; mRNA. DR EMBL; BC010664; AAH10664.1; -; mRNA. DR EMBL; BC110815; AAI10816.1; -; mRNA. DR EMBL; BC136763; AAI36764.1; -; mRNA. DR EMBL; AF218025; AAG17267.1; ALT_FRAME; mRNA. DR CCDS; CCDS44877.1; -. [Q9UHB6-4] DR CCDS; CCDS55826.1; -. [Q9UHB6-5] DR CCDS; CCDS58230.1; -. [Q9UHB6-3] DR CCDS; CCDS8802.1; -. [Q9UHB6-1] DR RefSeq; NP_001107018.1; NM_001113546.1. [Q9UHB6-4] DR RefSeq; NP_001107019.1; NM_001113547.1. [Q9UHB6-5] DR RefSeq; NP_001230704.1; NM_001243775.1. [Q9UHB6-3] DR RefSeq; NP_057441.1; NM_016357.4. [Q9UHB6-1] DR RefSeq; XP_011536757.1; XM_011538455.2. DR RefSeq; XP_016874919.1; XM_017019430.1. DR PDB; 2D8Y; NMR; -; A=381-457. DR PDBsum; 2D8Y; -. DR AlphaFoldDB; Q9UHB6; -. DR SMR; Q9UHB6; -. DR BioGRID; 119559; 451. DR DIP; DIP-29633N; -. DR IntAct; Q9UHB6; 248. DR MINT; Q9UHB6; -. DR STRING; 9606.ENSP00000378400; -. DR GlyGen; Q9UHB6; 8 sites, 1 O-linked glycan (8 sites). DR iPTMnet; Q9UHB6; -. DR MetOSite; Q9UHB6; -. DR PhosphoSitePlus; Q9UHB6; -. DR SwissPalm; Q9UHB6; -. DR BioMuta; LIMA1; -. DR DMDM; 20138067; -. DR EPD; Q9UHB6; -. DR jPOST; Q9UHB6; -. DR MassIVE; Q9UHB6; -. DR MaxQB; Q9UHB6; -. DR PaxDb; 9606-ENSP00000378400; -. DR PeptideAtlas; Q9UHB6; -. DR ProteomicsDB; 84296; -. [Q9UHB6-1] DR ProteomicsDB; 84297; -. [Q9UHB6-2] DR ProteomicsDB; 84298; -. [Q9UHB6-3] DR ProteomicsDB; 84299; -. [Q9UHB6-4] DR Pumba; Q9UHB6; -. DR Antibodypedia; 14200; 385 antibodies from 33 providers. DR DNASU; 51474; -. DR Ensembl; ENST00000341247.9; ENSP00000340184.4; ENSG00000050405.14. [Q9UHB6-1] DR Ensembl; ENST00000394943.7; ENSP00000378400.3; ENSG00000050405.14. [Q9UHB6-4] DR Ensembl; ENST00000547825.5; ENSP00000448706.1; ENSG00000050405.14. [Q9UHB6-3] DR Ensembl; ENST00000552783.5; ENSP00000448779.1; ENSG00000050405.14. [Q9UHB6-5] DR Ensembl; ENST00000552823.5; ENSP00000450266.1; ENSG00000050405.14. [Q9UHB6-2] DR GeneID; 51474; -. DR KEGG; hsa:51474; -. DR MANE-Select; ENST00000341247.9; ENSP00000340184.4; NM_016357.5; NP_057441.1. DR UCSC; uc001rwg.5; human. [Q9UHB6-1] DR AGR; HGNC:24636; -. DR CTD; 51474; -. DR DisGeNET; 51474; -. DR GeneCards; LIMA1; -. DR HGNC; HGNC:24636; LIMA1. DR HPA; ENSG00000050405; Low tissue specificity. DR MalaCards; LIMA1; -. DR MIM; 608364; gene. DR MIM; 618079; phenotype. DR neXtProt; NX_Q9UHB6; -. DR OpenTargets; ENSG00000050405; -. DR PharmGKB; PA143485527; -. DR VEuPathDB; HostDB:ENSG00000050405; -. DR eggNOG; KOG1700; Eukaryota. DR GeneTree; ENSGT00940000158313; -. DR HOGENOM; CLU_021314_1_0_1; -. DR InParanoid; Q9UHB6; -. DR OMA; NQQVFHV; -. DR OrthoDB; 7294at2759; -. DR PhylomeDB; Q9UHB6; -. DR TreeFam; TF350273; -. DR PathwayCommons; Q9UHB6; -. DR SignaLink; Q9UHB6; -. DR SIGNOR; Q9UHB6; -. DR BioGRID-ORCS; 51474; 16 hits in 1158 CRISPR screens. DR ChiTaRS; LIMA1; human. DR EvolutionaryTrace; Q9UHB6; -. DR GeneWiki; LIMA1; -. DR GenomeRNAi; 51474; -. DR Pharos; Q9UHB6; Tbio. DR PRO; PR:Q9UHB6; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9UHB6; Protein. DR Bgee; ENSG00000050405; Expressed in oocyte and 204 other cell types or tissues. DR ExpressionAtlas; Q9UHB6; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IDA:LIFEdb. DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB. DR GO; GO:0032154; C:cleavage furrow; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005925; C:focal adhesion; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0001726; C:ruffle; ISS:UniProtKB. DR GO; GO:0001725; C:stress fiber; IDA:UniProtKB. DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB. DR GO; GO:0003785; F:actin monomer binding; IDA:UniProtKB. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0051017; P:actin filament bundle assembly; IDA:UniProtKB. DR GO; GO:0016477; P:cell migration; ISS:UniProtKB. DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB. DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW. DR GO; GO:0030299; P:intestinal cholesterol absorption; ISS:UniProtKB. DR GO; GO:0030835; P:negative regulation of actin filament depolymerization; IDA:UniProtKB. DR GO; GO:0031529; P:ruffle organization; IDA:UniProtKB. DR CDD; cd09485; LIM_Eplin_alpha_beta; 1. DR Gene3D; 2.10.110.10; Cysteine Rich Protein; 1. DR InterPro; IPR028740; EPLIN_Lim_dom. DR InterPro; IPR001781; Znf_LIM. DR PANTHER; PTHR24206:SF57; LIM DOMAIN AND ACTIN-BINDING PROTEIN 1; 1. DR PANTHER; PTHR24206; OS06G0237300 PROTEIN; 1. DR Pfam; PF00412; LIM; 1. DR SMART; SM00132; LIM; 1. DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 2. DR PROSITE; PS00478; LIM_DOMAIN_1; 1. DR PROSITE; PS50023; LIM_DOMAIN_2; 1. DR Genevisible; Q9UHB6; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Actin-binding; Alternative promoter usage; KW Alternative splicing; Cell junction; Cell membrane; Cholesterol metabolism; KW Cytoplasm; Cytoskeleton; LIM domain; Lipid metabolism; Membrane; KW Metal-binding; Phosphoprotein; Reference proteome; Steroid metabolism; KW Sterol metabolism; Zinc. FT CHAIN 1..759 FT /note="LIM domain and actin-binding protein 1" FT /id="PRO_0000075730" FT DOMAIN 388..448 FT /note="LIM zinc-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125" FT REGION 78..131 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 146..182 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 211..264 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 323..381 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 493..513 FT /note="Required for interaction with MYO5B" FT /evidence="ECO:0000250|UniProtKB:Q9ERG0" FT REGION 509..709 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 164..166 FT /note="Required for interaction with NPC1L1" FT /evidence="ECO:0000250|UniProtKB:Q9ERG0" FT COMPBIAS 91..106 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 211..227 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 248..264 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 323..337 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 513..527 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 552..586 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 587..607 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 626..640 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 641..656 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 657..675 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 695..709 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 4 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 15 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 55 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 132 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17924679, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 225 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569" FT MOD_RES 229 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 230 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9ERG0" FT MOD_RES 242 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9ERG0" FT MOD_RES 263 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 343 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 350 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 362 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" FT MOD_RES 369 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 374 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 439 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9ERG0" FT MOD_RES 490 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 601 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 604 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 609 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 617 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 692 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:20068231" FT MOD_RES 698 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 726 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 741 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9ERG0" FT VAR_SEQ 1..302 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10931946, FT ECO:0000303|PubMed:14702039" FT /id="VSP_003117" FT VAR_SEQ 1..160 FT /note="Missing (in isoform Alpha and isoform 5)" FT /evidence="ECO:0000303|PubMed:10618726, FT ECO:0000303|PubMed:14702039" FT /id="VSP_003116" FT VAR_SEQ 344 FT /note="R -> PG (in isoform 4 and isoform 5)" FT /evidence="ECO:0000303|PubMed:10931946, ECO:0000303|Ref.5" FT /id="VSP_040136" FT VARIANT 25 FT /note="L -> I (correlated with lower plasma levels of FT low-density lipoprotein cholesterol; reduces protein FT stability; dbSNP:rs140372565)" FT /evidence="ECO:0000269|PubMed:29880681" FT /id="VAR_080864" FT CONFLICT 381 FT /note="Missing (in Ref. 4; BAA90914 and 7; AAH01247)" FT /evidence="ECO:0000305" FT CONFLICT 415 FT /note="F -> L (in Ref. 8; AAG17267)" FT /evidence="ECO:0000305" FT CONFLICT 463 FT /note="D -> G (in Ref. 4; BAA90914)" FT /evidence="ECO:0000305" FT CONFLICT 491 FT /note="P -> Q (in Ref. 2; AAF67491)" FT /evidence="ECO:0000305" FT CONFLICT 520..521 FT /note="DK -> NR (in Ref. 2; AAF67491)" FT /evidence="ECO:0000305" FT STRAND 384..387 FT /evidence="ECO:0007829|PDB:2D8Y" FT TURN 391..393 FT /evidence="ECO:0007829|PDB:2D8Y" FT STRAND 401..404 FT /evidence="ECO:0007829|PDB:2D8Y" FT STRAND 406..411 FT /evidence="ECO:0007829|PDB:2D8Y" FT TURN 412..414 FT /evidence="ECO:0007829|PDB:2D8Y" FT TURN 418..420 FT /evidence="ECO:0007829|PDB:2D8Y" FT TURN 426..428 FT /evidence="ECO:0007829|PDB:2D8Y" FT STRAND 432..434 FT /evidence="ECO:0007829|PDB:2D8Y" FT HELIX 439..445 FT /evidence="ECO:0007829|PDB:2D8Y" FT MOD_RES Q9UHB6-2:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES Q9UHB6-4:343 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES Q9UHB6-5:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES Q9UHB6-5:183 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" SQ SEQUENCE 759 AA; 85226 MW; 996378AFD3B003D5 CRC64; MESSPFNRRQ WTSLSLRVTA KELSLVNKNK SSAIVEIFSK YQKAAEETNM EKKRSNTENL SQHFRKGTLT VLKKKWENPG LGAESHTDSL RNSSTEIRHR ADHPPAEVTS HAASGAKADQ EEQIHPRSRL RSPPEALVQG RYPHIKDGED LKDHSTESKK MENCLGESRH EVEKSEISEN TDASGKIEKY NVPLNRLKMM FEKGEPTQTK ILRAQSRSAS GRKISENSYS LDDLEIGPGQ LSSSTFDSEK NESRRNLELP RLSETSIKDR MAKYQAAVSK QSSSTNYTNE LKASGGEIKI HKMEQKENVP PGPEVCITHQ EGEKISANEN SLAVRSTPAE DDSRDSQVKS EVQQPVHPKP LSPDSRASSL SESSPPKAMK KFQAPARETC VECQKTVYPM ERLLANQQVF HISCFRCSYC NNKLSLGTYA SLHGRIYCKP HFNQLFKSKG NYDEGFGHRP HKDLWASKNE NEEILERPAQ LANARETPHS PGVEDAPIAK VGVLAASMEA KASSQQEKED KPAETKKLRI AWPPPTELGS SGSALEEGIK MSKPKWPPED EISKPEVPED VDLDLKKLRR SSSLKERSRP FTVAASFQST SVKSPKTVSP PIRKGWSMSE QSEESVGGRV AERKQVENAK ASKKNGNVGK TTWQNKESKG ETGKRSKEGH SLEMENENLV ENGADSDEDD NSFLKQQSPQ EPKSLNWSSF VDNTFAEEFT TQNQKSQDVE LWEGEVVKEL SVEEQIKRNR YYDEDEDEE //