ID MOES_HUMAN Reviewed; 577 AA. AC P26038; DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 245. DE RecName: Full=Moesin {ECO:0000303|PubMed:1924289}; DE AltName: Full=Membrane-organizing extension spike protein; GN Name=MSN {ECO:0000312|HGNC:HGNC:7373}; 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], AND PROTEIN SEQUENCE OF 2-16; 54-60 AND RP 414-435. RC TISSUE=Placenta; RX PubMed=1924289; DOI=10.1073/pnas.88.19.8297; RA Lankes W.T., Furthmayr H.; RT "Moesin: a member of the protein 4.1-talin-ezrin family of proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 88:8297-8301(1991). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 2-8. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [5] RP INTERACTION WITH CD46, AND SUBCELLULAR LOCATION. RX PubMed=7884872; DOI=10.1128/jvi.69.4.2248-2256.1995; RA Schneider-Schaulies J., Dunster L.M., Schwartz-Albiez R., Krohne G., RA ter Meulen V.; RT "Physical association of moesin and CD46 as a receptor complex for measles RT virus."; RL J. Virol. 69:2248-2256(1995). RN [6] RP INTERACTION WITH NHERF1. RX PubMed=9314537; DOI=10.1083/jcb.139.1.169; RA Reczek D., Berryman M., Bretscher A.; RT "Identification of EBP50: a PDZ-containing phosphoprotein that associates RT with members of the ezrin-radixin-moesin family."; RL J. Cell Biol. 139:169-179(1997). RN [7] RP INTERACTION WITH HIV-1 ENVELOPE PROTEIN GP120. RX PubMed=9213396; DOI=10.1016/s0168-1702(97)00039-7; RA Hecker C., Weise C., Schneider-Schaulies J., Holmes H.C., ter Meulen V.; RT "Specific binding of HIV-1 envelope protein gp120 to the structural RT membrane proteins ezrin and moesin."; RL Virus Res. 49:215-223(1997). RN [8] RP FUNCTION, INTERACTION WITH ICAM3 AND CD44, AND SUBCELLULAR LOCATION. RX PubMed=9298994; DOI=10.1083/jcb.138.6.1409; RA Serrador J.M., Alonso-Lebrero J.L., del Pozo M.A., Furthmayr H., RA Schwartz-Albiez R., Calvo J., Lozano F., Sanchez-Madrid F.; RT "Moesin interacts with the cytoplasmic region of intercellular adhesion RT molecule-3 and is redistributed to the uropod of T lymphocytes during cell RT polarization."; RL J. Cell Biol. 138:1409-1423(1997). RN [9] RP FUNCTION, AND INTERACTION WITH SPN/CD43 CYTOPLASMIC TAIL. RX PubMed=9616160; RA Serrador J.M., Nieto M., Alonso-Lebrero J.L., del Pozo M.A., Calvo J., RA Furthmayr H., Schwartz-Albiez R., Lozano F., Gonzalez-Amaro R., RA Sanchez-Mateos P., Sanchez-Madrid F.; RT "CD43 interacts with moesin and ezrin and regulates its redistribution to RT the uropods of T lymphocytes at the cell-cell contacts."; RL Blood 91:4632-4644(1998). RN [10] RP FUNCTION, MUTAGENESIS OF THR-558, AND INTERACTION WITH F-ACTIN. RX PubMed=10212266; DOI=10.1074/jbc.274.18.12803; RA Huang L., Wong T.Y., Lin R.C., Furthmayr H.; RT "Replacement of threonine 558, a critical site of phosphorylation of moesin RT in vivo, with aspartate activates F-actin binding of moesin. Regulation by RT conformational change."; RL J. Biol. Chem. 274:12803-12810(1999). RN [11] RP FUNCTION, INTERACTION WITH SPN/CD43 CYTOPLASMIC TAIL, AND SUBCELLULAR RP LOCATION. RX PubMed=11728332; DOI=10.1016/s1074-7613(01)00231-x; RA Delon J., Kaibuchi K., Germain R.N.; RT "Exclusion of CD43 from the immunological synapse is mediated by RT phosphorylation-regulated relocation of the cytoskeletal adaptor moesin."; RL Immunity 15:691-701(2001). RN [12] RP INTERACTION WITH SELPLG AND SYK, AND FUNCTION. RX PubMed=12387735; DOI=10.1016/s1074-7613(02)00420-x; RA Urzainqui A., Serrador J.M., Viedma F., Yanez-Mo M., Rodriguez A., RA Corbi A.L., Alonso-Lebrero J.L., Luque A., Deckert M., Vazquez J., RA Sanchez-Madrid F.; RT "ITAM-based interaction of ERM proteins with Syk mediates signaling by the RT leukocyte adhesion receptor PSGL-1."; RL Immunity 17:401-412(2002). RN [13] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15039356; DOI=10.1128/iai.72.4.2312-2320.2004; RA Iontcheva I., Amar S., Zawawi K.H., Kantarci A., Van Dyke T.E.; RT "Role for moesin in lipopolysaccharide-stimulated signal transduction."; RL Infect. Immun. 72:2312-2320(2004). RN [14] RP INTERACTION WITH PDPN. RX PubMed=17046996; DOI=10.1242/jcs.03218; RA Martin-Villar E., Megias D., Castel S., Yurrita M.M., Vilaro S., RA Quintanilla M.; RT "Podoplanin binds ERM proteins to activate RhoA and promote epithelial- RT mesenchymal transition."; RL J. Cell Sci. 119:4541-4553(2006). RN [15] RP SUBCELLULAR LOCATION, AND INTERACTION WITH PPP1R16B. RX PubMed=18586956; DOI=10.1152/ajplung.00325.2007; RA Csortos C., Czikora I., Bogatcheva N.V., Adyshev D.M., Poirier C., Olah G., RA Verin A.D.; RT "TIMAP is a positive regulator of pulmonary endothelial barrier function."; RL Am. J. Physiol. 295:L440-L450(2008). RN [16] 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 [17] RP PHOSPHORYLATION AT THR-558, AND MUTAGENESIS OF TYR-556 AND THR-558. RX PubMed=19255442; DOI=10.1073/pnas.0805963106; RA Belkina N.V., Liu Y., Hao J.J., Karasuyama H., Shaw S.; RT "LOK is a major ERM kinase in resting lymphocytes and regulates RT cytoskeletal rearrangement through ERM phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 106:4707-4712(2009). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-116, AND IDENTIFICATION BY RP 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 LYS-79 AND LYS-139, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). 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 FUNCTION, AND INTERACTION WITH PDZD8. RX PubMed=21549406; DOI=10.1016/j.virol.2011.04.006; RA Henning M.S., Stiedl P., Barry D.S., McMahon R., Morham S.G., Walsh D., RA Naghavi M.H.; RT "PDZD8 is a novel moesin-interacting cytoskeletal regulatory protein that RT suppresses infection by herpes simplex virus type 1."; RL Virology 415:114-121(2011). RN [22] 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-74; SER-407 AND SER-527, AND RP 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 S-NITROSYLATION AT CYS-117, MUTAGENESIS OF ILE-115 AND GLU-120, AND DOMAIN. RX PubMed=25417112; DOI=10.1016/j.cell.2014.09.032; RA Jia J., Arif A., Terenzi F., Willard B., Plow E.F., Hazen S.L., Fox P.L.; RT "Target-selective protein S-nitrosylation by sequence motif recognition."; RL Cell 159:623-634(2014). RN [25] RP IDENTIFICATION BY 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 [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [27] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 4-577. RX PubMed=10847681; DOI=10.1016/s0092-8674(00)80836-3; RA Pearson M.A., Reczek D., Bretscher A., Karplus P.A.; RT "Structure of the ERM protein moesin reveals the FERM domain fold masked by RT an extended actin binding tail domain."; RL Cell 101:259-270(2000). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-346. RX PubMed=11401550; DOI=10.1021/bi010419h; RA Edwards S.D., Keep N.H.; RT "The 2.7 A crystal structure of the activated FERM domain of moesin: an RT analysis of structural changes on activation."; RL Biochemistry 40:7061-7068(2001). RN [29] RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 1-297 IN COMPLEX WITH NHERF1. RX PubMed=15020681; DOI=10.1242/jcs.01038; RA Finnerty C.M., Chambers D., Ingraffea J., Faber H.R., Karplus P.A., RA Bretscher A.; RT "The EBP50-moesin interaction involves a binding site regulated by direct RT masking on the FERM domain."; RL J. Cell Sci. 117:1547-1552(2004). RN [30] RP VARIANT IMD50 TRP-171, CHARACTERIZATION OF VARIANT IMD50 TRP-171, AND RP FUNCTION. RX PubMed=27405666; DOI=10.1016/j.jaci.2016.04.032; RA Lagresle-Peyrou C., Luce S., Ouchani F., Soheili T.S., Sadek H., RA Chouteau M., Durand A., Pic I., Majewski J., Brouzes C., Lambert N., RA Bohineust A., Verhoeyen E., Cosset F.L., Magerus-Chatinet A., RA Rieux-Laucat F., Gandemer V., Monnier D., Heijmans C., van Gijn M., RA Dalm V.A., Mahlaoui N., Stephan J.L., Picard C., Durandy A., Kracker S., RA Hivroz C., Jabado N., de Saint Basile G., Fischer A., Cavazzana M., RA Andre-Schmutz I.; RT "X-linked primary immunodeficiency associated with hemizygous mutations in RT the moesin (MSN) gene."; RL J. Allergy Clin. Immunol. 138:1681-1689(2016). CC -!- FUNCTION: Ezrin-radixin-moesin (ERM) family protein that connects the CC actin cytoskeleton to the plasma membrane and thereby regulates the CC structure and function of specific domains of the cell cortex. Tethers CC actin filaments by oscillating between a resting and an activated state CC providing transient interactions between moesin and the actin CC cytoskeleton (PubMed:10212266). Once phosphorylated on its C-terminal CC threonine, moesin is activated leading to interaction with F-actin and CC cytoskeletal rearrangement (PubMed:10212266). These rearrangements CC regulate many cellular processes, including cell shape determination, CC membrane transport, and signal transduction (PubMed:12387735, CC PubMed:15039356). The role of moesin is particularly important in CC immunity acting on both T and B-cells homeostasis and self-tolerance, CC regulating lymphocyte egress from lymphoid organs (PubMed:9298994, CC PubMed:9616160). Modulates phagolysosomal biogenesis in macrophages (By CC similarity). Participates also in immunologic synapse formation CC (PubMed:27405666). {ECO:0000250|UniProtKB:P26041, CC ECO:0000269|PubMed:10212266, ECO:0000269|PubMed:12387735, CC ECO:0000269|PubMed:15039356, ECO:0000269|PubMed:27405666, CC ECO:0000269|PubMed:9298994, ECO:0000269|PubMed:9616160}. CC -!- ACTIVITY REGULATION: A head-to-tail association, of the N-terminal and CC C-terminal halves results in a closed conformation (inactive form) CC which is incapable of actin or membrane-binding. CC {ECO:0000269|PubMed:10212266}. CC -!- SUBUNIT: In resting T-cells, part of a PAG1-NHERF1-MSN complex which is CC disrupted upon TCR activation. Interacts with NHERF1 (PubMed:9314537, CC PubMed:15020681). Interacts with PPP1R16B (PubMed:18586956). Interacts CC with SELPLG and SYK; these interactions mediate the activation of SYK CC by SELPLG (PubMed:12387735). Interacts with PDPN (via cytoplasmic CC domain); this interaction activates RHOA and promotes epithelial- CC mesenchymal transition (PubMed:17046996). Interacts with SPN/CD43 CC cytoplasmic tail (PubMed:9616160, PubMed:11728332). Interacts with CD44 CC (PubMed:9298994). Interacts with ICAM2 (By similarity). Interacts with CC ICAM3 (via C-terminus) (PubMed:9298994). Interacts with PDZD8 CC (PubMed:21549406). Interacts with F-actin (PubMed:10212266). Interacts CC with CD46 (PubMed:7884872). Interacts with PTPN6 (By similarity). CC {ECO:0000250|UniProtKB:P26041, ECO:0000269|PubMed:10212266, CC ECO:0000269|PubMed:11728332, ECO:0000269|PubMed:12387735, CC ECO:0000269|PubMed:15020681, ECO:0000269|PubMed:17046996, CC ECO:0000269|PubMed:18586956, ECO:0000269|PubMed:21549406, CC ECO:0000269|PubMed:7884872, ECO:0000269|PubMed:9298994, CC ECO:0000269|PubMed:9314537, ECO:0000269|PubMed:9616160}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 envelope protein CC gp120. {ECO:0000269|PubMed:9213396}. CC -!- INTERACTION: CC P26038; P16070: CD44; NbExp=6; IntAct=EBI-528768, EBI-490245; CC P26038; P25791-3: LMO2; NbExp=3; IntAct=EBI-528768, EBI-11959475; CC P26038; Q5S007: LRRK2; NbExp=19; IntAct=EBI-528768, EBI-5323863; CC P26038; O14745: NHERF1; NbExp=4; IntAct=EBI-528768, EBI-349787; CC P26038; P54274: TERF1; NbExp=2; IntAct=EBI-528768, EBI-710997; CC P26038; Q5S006: Lrrk2; Xeno; NbExp=2; IntAct=EBI-528768, EBI-2693710; CC P26038; P97820: Map4k4; Xeno; NbExp=2; IntAct=EBI-528768, EBI-644181; CC P26038; P0DTC2: S; Xeno; NbExp=20; IntAct=EBI-528768, EBI-25474821; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11728332, CC ECO:0000269|PubMed:15039356, ECO:0000269|PubMed:18586956, CC ECO:0000269|PubMed:7884872, ECO:0000269|PubMed:9298994}; Peripheral CC membrane protein {ECO:0000250|UniProtKB:P26041}; Cytoplasmic side CC {ECO:0000250|UniProtKB:P26041}. Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:P26041}. Apical cell membrane CC {ECO:0000250|UniProtKB:P26041}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P26041}; Cytoplasmic side CC {ECO:0000250|UniProtKB:P26041}. Cell projection, microvillus membrane CC {ECO:0000250|UniProtKB:P26041}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P26041}; Cytoplasmic side CC {ECO:0000250|UniProtKB:P26041}. Cell projection, microvillus CC {ECO:0000250|UniProtKB:P26041}. Note=Phosphorylated form is enriched in CC microvilli-like structures at apical membrane. Increased cell membrane CC localization of both phosphorylated and non-phosphorylated forms seen CC after thrombin treatment (By similarity). Localizes at the uropods of T CC lymphoblasts. {ECO:0000250|UniProtKB:P26041, CC ECO:0000269|PubMed:18586956, ECO:0000269|PubMed:9298994}. CC -!- TISSUE SPECIFICITY: In all tissues and cultured cells studied. CC -!- DOMAIN: The [IL]-x-C-x-x-[DE] motif is a proposed target motif for CC cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 CC transnitrosylase complex. {ECO:0000305|PubMed:25417112}. CC -!- PTM: Phosphorylation on Thr-558 is crucial for the formation of CC microvilli-like structures. Phosphorylation by ROCK2 suppresses the CC head-to-tail association of the N-terminal and C-terminal halves CC resulting in an opened conformation which is capable of actin and CC membrane-binding (By similarity). Phosphorylation on Thr-558 by STK10 CC negatively regulates lymphocyte migration and polarization. CC {ECO:0000250, ECO:0000269|PubMed:19255442}. CC -!- PTM: S-nitrosylation of Cys-117 is induced by interferon-gamma and CC oxidatively-modified low-densitity lipoprotein (LDL(ox)) implicating CC the iNOS-S100A8/9 transnitrosylase complex. CC {ECO:0000269|PubMed:25417112}. CC -!- DISEASE: Immunodeficiency 50 (IMD50) [MIM:300988]: A primary CC immunodeficiency disorder characterized by onset of recurrent bacterial CC or varicella zoster virus infections in early childhood, profound CC lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and CC neutropenia, and a poor immune response to vaccine antigens. CC {ECO:0000269|PubMed:27405666}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/363/MSN"; 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; M69066; AAA36322.1; -; mRNA. DR EMBL; Z98946; CAB46379.1; -; Genomic_DNA. DR EMBL; BC017293; AAH17293.1; -; mRNA. DR CCDS; CCDS14382.1; -. DR PIR; A41289; A41289. DR RefSeq; NP_002435.1; NM_002444.2. DR PDB; 1E5W; X-ray; 2.70 A; A=2-346. DR PDB; 1EF1; X-ray; 1.90 A; A/B=4-297, C/D=488-577. DR PDB; 1SGH; X-ray; 3.50 A; A=1-297. DR PDB; 6TXQ; X-ray; 1.73 A; AAA=1-346. DR PDB; 6TXS; X-ray; 2.20 A; AAA=1-346. DR PDB; 8CIR; X-ray; 1.85 A; A/B=1-346. DR PDB; 8CIS; X-ray; 1.52 A; A=1-346. DR PDB; 8CIT; X-ray; 2.54 A; A/B/C=1-346. DR PDB; 8CIU; X-ray; 2.39 A; A=1-346. DR PDBsum; 1E5W; -. DR PDBsum; 1EF1; -. DR PDBsum; 1SGH; -. DR PDBsum; 6TXQ; -. DR PDBsum; 6TXS; -. DR PDBsum; 8CIR; -. DR PDBsum; 8CIS; -. DR PDBsum; 8CIT; -. DR PDBsum; 8CIU; -. DR AlphaFoldDB; P26038; -. DR SMR; P26038; -. DR BioGRID; 110584; 285. DR DIP; DIP-33841N; -. DR IntAct; P26038; 71. DR MINT; P26038; -. DR STRING; 9606.ENSP00000353408; -. DR ChEMBL; CHEMBL4295733; -. DR GlyGen; P26038; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P26038; -. DR MetOSite; P26038; -. DR PhosphoSitePlus; P26038; -. DR SwissPalm; P26038; -. DR BioMuta; MSN; -. DR DMDM; 127234; -. DR OGP; P26038; -. DR CPTAC; CPTAC-94; -. DR EPD; P26038; -. DR jPOST; P26038; -. DR MassIVE; P26038; -. DR PaxDb; 9606-ENSP00000353408; -. DR PeptideAtlas; P26038; -. DR PRIDE; P26038; -. DR ProteomicsDB; 54311; -. DR Pumba; P26038; -. DR TopDownProteomics; P26038; -. DR Antibodypedia; 2774; 1121 antibodies from 43 providers. DR CPTC; P26038; 3 antibodies. DR DNASU; 4478; -. DR Ensembl; ENST00000360270.7; ENSP00000353408.5; ENSG00000147065.18. DR GeneID; 4478; -. DR KEGG; hsa:4478; -. DR MANE-Select; ENST00000360270.7; ENSP00000353408.5; NM_002444.3; NP_002435.1. DR AGR; HGNC:7373; -. DR CTD; 4478; -. DR DisGeNET; 4478; -. DR GeneCards; MSN; -. DR HGNC; HGNC:7373; MSN. DR HPA; ENSG00000147065; Low tissue specificity. DR MalaCards; MSN; -. DR MIM; 300988; phenotype. DR MIM; 309845; gene. DR neXtProt; NX_P26038; -. DR OpenTargets; ENSG00000147065; -. DR Orphanet; 504530; Combined immunodeficiency due to Moesin deficiency. DR PharmGKB; PA31178; -. DR VEuPathDB; HostDB:ENSG00000147065; -. DR eggNOG; KOG3529; Eukaryota. DR GeneTree; ENSGT01090000260082; -. DR HOGENOM; CLU_003623_6_2_1; -. DR InParanoid; P26038; -. DR OMA; QWEDRIH; -. DR OrthoDB; 5476297at2759; -. DR PhylomeDB; P26038; -. DR TreeFam; TF313935; -. DR PathwayCommons; P26038; -. DR Reactome; R-HSA-437239; Recycling pathway of L1. DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation. DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea. DR Reactome; R-HSA-9662361; Sensory processing of sound by outer hair cells of the cochlea. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR SignaLink; P26038; -. DR SIGNOR; P26038; -. DR BioGRID-ORCS; 4478; 20 hits in 780 CRISPR screens. DR ChiTaRS; MSN; human. DR EvolutionaryTrace; P26038; -. DR GeneWiki; Moesin; -. DR GenomeRNAi; 4478; -. DR Pharos; P26038; Tbio. DR PRO; PR:P26038; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P26038; Protein. DR Bgee; ENSG00000147065; Expressed in lower lobe of lung and 212 other cell types or tissues. DR ExpressionAtlas; P26038; baseline and differential. DR GO; GO:0005912; C:adherens junction; IBA:GO_Central. DR GO; GO:0045177; C:apical part of cell; IDA:BHF-UCL. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0071944; C:cell periphery; IDA:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:CAFA. DR GO; GO:0005737; C:cytoplasm; HDA:UniProtKB. DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0030175; C:filopodium; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0005902; C:microvillus; IDA:BHF-UCL. DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0031143; C:pseudopodium; IDA:UniProtKB. DR GO; GO:0001931; C:uropod; IEA:Ensembl. DR GO; GO:0031982; C:vesicle; HDA:UniProtKB. DR GO; GO:0003779; F:actin binding; IBA:GO_Central. DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:BHF-UCL. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI. DR GO; GO:0019899; F:enzyme binding; IPI:CAFA. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc. DR GO; GO:0071394; P:cellular response to testosterone stimulus; IDA:UniProtKB. DR GO; GO:0061028; P:establishment of endothelial barrier; IGI:UniProtKB. DR GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; IMP:UniProtKB. DR GO; GO:0022612; P:gland morphogenesis; IMP:UniProtKB. DR GO; GO:0001771; P:immunological synapse formation; IDA:UniProtKB. DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IEP:BHF-UCL. DR GO; GO:0050900; P:leukocyte migration; IEP:BHF-UCL. DR GO; GO:0022614; P:membrane to membrane docking; IEP:BHF-UCL. DR GO; GO:2000643; P:positive regulation of early endosome to late endosome transport; IGI:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IGI:UniProtKB. DR GO; GO:0071803; P:positive regulation of podosome assembly; IEA:Ensembl. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IGI:UniProtKB. DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; IGI:UniProtKB. DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB. DR GO; GO:0008361; P:regulation of cell size; IMP:UniProtKB. DR GO; GO:2000401; P:regulation of lymphocyte migration; IMP:UniProtKB. DR GO; GO:1902115; P:regulation of organelle assembly; IGI:UniProtKB. DR GO; GO:0070489; P:T cell aggregation; IDA:UniProtKB. DR GO; GO:0072678; P:T cell migration; IDA:UniProtKB. DR GO; GO:0042098; P:T cell proliferation; IDA:UniProtKB. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd13194; FERM_C_ERM; 1. DR CDD; cd17187; FERM_F1_ERM; 1. DR Gene3D; 1.20.5.450; -; 1. DR Gene3D; 1.20.80.10; -; 1. DR Gene3D; 6.10.360.10; -; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR IDEAL; IID00344; -. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR011174; ERM. DR InterPro; IPR011259; ERM_C_dom. DR InterPro; IPR041789; ERM_FERM_C. DR InterPro; IPR046810; ERM_helical. DR InterPro; IPR000798; Ez/rad/moesin-like. DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR019747; FERM_CS. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR018979; FERM_N. DR InterPro; IPR018980; FERM_PH-like_C. DR InterPro; IPR008954; Moesin_tail_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR23281; MERLIN/MOESIN/EZRIN/RADIXIN; 1. DR PANTHER; PTHR23281:SF26; MOESIN; 1. DR Pfam; PF00769; ERM_C; 1. DR Pfam; PF20492; ERM_helical; 1. DR Pfam; PF09380; FERM_C; 1. DR Pfam; PF00373; FERM_M; 1. DR Pfam; PF09379; FERM_N; 1. DR PIRSF; PIRSF002305; ERM; 1. DR PRINTS; PR00935; BAND41. DR PRINTS; PR00661; ERMFAMILY. DR SMART; SM00295; B41; 1. DR SMART; SM01196; FERM_C; 1. DR SUPFAM; SSF48678; Moesin tail domain; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS00660; FERM_1; 1. DR PROSITE; PS00661; FERM_2; 1. DR PROSITE; PS50057; FERM_3; 1. DR Genevisible; P26038; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell membrane; Cell projection; Cytoplasm; KW Cytoskeleton; Direct protein sequencing; Disease variant; KW Host-virus interaction; Membrane; Phosphoprotein; Reference proteome; KW S-nitrosylation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0000269|PubMed:1924289" FT CHAIN 2..577 FT /note="Moesin" FT /id="PRO_0000219416" FT DOMAIN 2..295 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT REGION 323..342 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 375..409 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 466..518 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 115..120 FT /note="[IL]-x-C-x-x-[DE] motif" FT /evidence="ECO:0000305|PubMed:25417112" FT COMPBIAS 488..518 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 74 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 79 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 83 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P26043" FT MOD_RES 116 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 117 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:25417112" FT MOD_RES 139 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 165 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P26041" FT MOD_RES 407 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 527 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 558 FT /note="Phosphothreonine; by ROCK2 and STK10" FT /evidence="ECO:0000269|PubMed:19255442" FT VARIANT 171 FT /note="R -> W (in IMD50; decreased protein abundance in T FT cell; loss of T cell proliferation after T cell activation; FT does not affect immunologic synapses formation; decreased T FT cell migration in response to activation by chemokines; FT increased T cell adhesion in response to activation by FT integrins; dbSNP:rs1057519074)" FT /evidence="ECO:0000269|PubMed:27405666" FT /id="VAR_078026" FT MUTAGEN 115 FT /note="I->M: Inhibits S-nitrosylation of Cys-117; when FT associated with M-120." FT /evidence="ECO:0000269|PubMed:25417112" FT MUTAGEN 120 FT /note="E->M: Inhibits S-nitrosylation of Cys-117; when FT associated with M-115." FT /evidence="ECO:0000269|PubMed:25417112" FT MUTAGEN 556 FT /note="Y->R: Impairs phosphorylation by STK10." FT /evidence="ECO:0000269|PubMed:19255442" FT MUTAGEN 558 FT /note="T->A: Abolishes phosphorylation by STK10." FT /evidence="ECO:0000269|PubMed:19255442" FT MUTAGEN 558 FT /note="T->D: Completely abolishes the interaction between FT N- and C-terminal domains." FT /evidence="ECO:0000269|PubMed:10212266" FT MUTAGEN 558 FT /note="T->D: Phosphomimetic mutant." FT /evidence="ECO:0000269|PubMed:19255442" FT STRAND 5..10 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 15..20 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 26..37 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 42..44 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 45..51 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 56..58 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 63..65 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 68..70 FT /evidence="ECO:0007829|PDB:8CIU" FT STRAND 74..82 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 89..92 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 96..111 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 119..134 FT /evidence="ECO:0007829|PDB:8CIS" FT TURN 139..141 FT /evidence="ECO:0007829|PDB:8CIS" FT TURN 144..149 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 155..160 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 165..178 FT /evidence="ECO:0007829|PDB:8CIS" FT TURN 179..181 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 184..195 FT /evidence="ECO:0007829|PDB:8CIS" FT TURN 199..202 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 204..210 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 215..221 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 224..229 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 233..235 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 237..241 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 242..244 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 245..251 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 254..261 FT /evidence="ECO:0007829|PDB:8CIS" FT STRAND 267..270 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 274..295 FT /evidence="ECO:0007829|PDB:8CIS" FT HELIX 300..311 FT /evidence="ECO:0007829|PDB:8CIS" FT TURN 334..337 FT /evidence="ECO:0007829|PDB:8CIU" FT HELIX 340..343 FT /evidence="ECO:0007829|PDB:8CIR" FT HELIX 504..507 FT /evidence="ECO:0007829|PDB:1EF1" FT HELIX 511..514 FT /evidence="ECO:0007829|PDB:1EF1" FT HELIX 516..530 FT /evidence="ECO:0007829|PDB:1EF1" FT HELIX 540..550 FT /evidence="ECO:0007829|PDB:1EF1" FT HELIX 555..562 FT /evidence="ECO:0007829|PDB:1EF1" FT HELIX 567..575 FT /evidence="ECO:0007829|PDB:1EF1" SQ SEQUENCE 577 AA; 67820 MW; 865A6C5CB14AE586 CRC64; MPKTISVRVT TMDAELEFAI QPNTTGKQLF DQVVKTIGLR EVWFFGLQYQ DTKGFSTWLK LNKKVTAQDV RKESPLLFKF RAKFYPEDVS EELIQDITQR LFFLQVKEGI LNDDIYCPPE TAVLLASYAV QSKYGDFNKE VHKSGYLAGD KLLPQRVLEQ HKLNKDQWEE RIQVWHEEHR GMLREDAVLE YLKIAQDLEM YGVNYFSIKN KKGSELWLGV DALGLNIYEQ NDRLTPKIGF PWSEIRNISF NDKKFVIKPI DKKAPDFVFY APRLRINKRI LALCMGNHEL YMRRRKPDTI EVQQMKAQAR EEKHQKQMER AMLENEKKKR EMAEKEKEKI EREKEELMER LKQIEEQTKK AQQELEEQTR RALELEQERK RAQSEAEKLA KERQEAEEAK EALLQASRDQ KKTQEQLALE MAELTARISQ LEMARQKKES EAVEWQQKAQ MVQEDLEKTR AELKTAMSTP HVAEPAENEQ DEQDENGAEA SADLRADAMA KDRSEEERTT EAEKNERVQK HLKALTSELA NARDESKKTA NDMIHAENMR LGRDKYKTLR QIRQGNTKQR IDEFESM //