Full text data of MSN
MSN
[Confidence: high (present in two of the MS resources)]
Moesin (Membrane-organizing extension spike protein)
Moesin (Membrane-organizing extension spike protein)
hRBCD
IPI00219365
IPI00219365 moesin moesin membrane n/a n/a n/a n/a n/a n/a n/a n/a 5 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoskeleton n/a expected molecular weight found in band > 200 kDa together with ubiquitin
IPI00219365 moesin moesin membrane n/a n/a n/a n/a n/a n/a n/a n/a 5 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoskeleton n/a expected molecular weight found in band > 200 kDa together with ubiquitin
UniProt
P26038
ID MOES_HUMAN Reviewed; 577 AA.
AC P26038;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Moesin;
DE AltName: Full=Membrane-organizing extension spike protein;
GN Name=MSN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA 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.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA 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.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA 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.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA 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.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., 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
RT project: 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.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [5]
RP INTERACTION WITH SLC9A3R1.
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
RT associates with members of the ezrin-radixin-moesin family.";
RL J. Cell Biol. 139:169-179(1997).
RN [6]
RP INTERACTION WITH SELPLG AND SYK.
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
RT the leukocyte adhesion receptor PSGL-1.";
RL Immunity 17:401-412(2002).
RN [7]
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.,
RA Olah G., Verin A.D.;
RT "TIMAP is a positive regulator of pulmonary endothelial barrier
RT function.";
RL Am. J. Physiol. 295:L440-L450(2008).
RN [8]
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 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-116, AND MASS
RP SPECTROMETRY.
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-79 AND LYS-139, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [12]
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.,
RA Buerckstuemmer T., 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 [13]
RP FUNCTION, AND INTERACTION WITH MSN.
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.,
RA Walsh D., Naghavi M.H.;
RT "PDZD8 is a novel moesin-interacting cytoskeletal regulatory protein
RT that suppresses infection by herpes simplex virus type 1.";
RL Virology 415:114-121(2011).
RN [14]
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
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
RT masked by an extended actin binding tail domain.";
RL Cell 101:259-270(2000).
RN [16]
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:
RT an analysis of structural changes on activation.";
RL Biochemistry 40:7061-7068(2001).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 1-297 IN COMPLEX WITH
RP SLC9A3R1.
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
RT direct masking on the FERM domain.";
RL J. Cell Sci. 117:1547-1552(2004).
CC -!- FUNCTION: Probably involved in connections of major cytoskeletal
CC structures to the plasma membrane. May inhibit herpes simplex
CC virus 1 infection at an early stage.
CC -!- ENZYME REGULATION: A head-to-tail association, of the N-terminal
CC and C-terminal halves results in a closed conformation (inactive
CC form) which is incapable of actin or membrane-binding (By
CC similarity).
CC -!- SUBUNIT: In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex
CC which is disrupted upon TCR activation (By similarity). Binds
CC SLC9A3R1. Interacts with PPP1R16B. Interacts with PDZD8. Interacts
CC with SELPLG and SYK; mediates the activation of SYK by SELPLG.
CC -!- INTERACTION:
CC Q5S007:LRRK2; NbExp=5; IntAct=EBI-528768, EBI-5323863;
CC O14745:SLC9A3R1; NbExp=5; IntAct=EBI-528768, EBI-349787;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side (By similarity). Cytoplasm, cytoskeleton (By
CC similarity). Apical cell membrane; Peripheral membrane protein;
CC Cytoplasmic side (By similarity). Cell projection, microvillus
CC membrane; Peripheral membrane protein; Cytoplasmic side (By
CC similarity). Note=Phosphorylated form is enriched in microvilli-
CC like structures at apical membrane (By similarity). Increased cell
CC membrane localization of both phosphorylated and non-
CC phosphorylated forms seen after thrombin treatment.
CC -!- TISSUE SPECIFICITY: In all tissues and cultured cells studied.
CC -!- PTM: Phosphorylation on Thr-558 is crucial for the formation of
CC microvilli-like structures. Phosphorylation by ROCK2 suppresses
CC the head-to-tail association of the N-terminal and C-terminal
CC halves resulting in an opened conformation which is capable of
CC actin and membrane-binding (By similarity). Phosphorylation on
CC Thr-558 by STK10 negatively regulates lymphocyte migration and
CC polarization.
CC -!- SIMILARITY: Contains 1 FERM domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MSNID363.html";
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DR EMBL; M69066; AAA36322.1; -; mRNA.
DR EMBL; Z98946; CAB46379.1; -; Genomic_DNA.
DR EMBL; BC017293; AAH17293.1; -; mRNA.
DR PIR; A41289; A41289.
DR RefSeq; NP_002435.1; NM_002444.2.
DR UniGene; Hs.87752; -.
DR PDB; 1E5W; X-ray; 2.70 A; A=1-346.
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 PDBsum; 1E5W; -.
DR PDBsum; 1EF1; -.
DR PDBsum; 1SGH; -.
DR ProteinModelPortal; P26038; -.
DR SMR; P26038; 1-577.
DR IntAct; P26038; 13.
DR MINT; MINT-3010439; -.
DR STRING; 9606.ENSP00000353408; -.
DR PhosphoSite; P26038; -.
DR DMDM; 127234; -.
DR OGP; P26038; -.
DR PaxDb; P26038; -.
DR PeptideAtlas; P26038; -.
DR PRIDE; P26038; -.
DR DNASU; 4478; -.
DR Ensembl; ENST00000360270; ENSP00000353408; ENSG00000147065.
DR GeneID; 4478; -.
DR KEGG; hsa:4478; -.
DR UCSC; uc004dwf.3; human.
DR CTD; 4478; -.
DR GeneCards; GC0XP064887; -.
DR HGNC; HGNC:7373; MSN.
DR HPA; CAB010898; -.
DR HPA; CAB047338; -.
DR HPA; HPA000263; -.
DR HPA; HPA000763; -.
DR HPA; HPA011135; -.
DR HPA; HPA011227; -.
DR MIM; 309845; gene.
DR neXtProt; NX_P26038; -.
DR PharmGKB; PA31178; -.
DR eggNOG; NOG236035; -.
DR HOGENOM; HOG000007113; -.
DR HOVERGEN; HBG002185; -.
DR InParanoid; P26038; -.
DR KO; K05763; -.
DR OMA; PHVTEPM; -.
DR OrthoDB; EOG7BGHK6; -.
DR PhylomeDB; P26038; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; MSN; human.
DR EvolutionaryTrace; P26038; -.
DR GeneWiki; Moesin; -.
DR GenomeRNAi; 4478; -.
DR NextBio; 17331; -.
DR PMAP-CutDB; P26038; -.
DR PRO; PR:P26038; -.
DR Bgee; P26038; -.
DR CleanEx; HS_MSN; -.
DR Genevestigator; P26038; -.
DR GO; GO:0045177; C:apical part of cell; IDA:BHF-UCL.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic to membrane; IEA:InterPro.
DR GO; GO:0030175; C:filopodium; IDA:BHF-UCL.
DR GO; GO:0005902; C:microvillus; IDA:BHF-UCL.
DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001931; C:uropod; IEA:Ensembl.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
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:2000401; P:regulation of lymphocyte migration; IMP:UniProtKB.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR019750; Band_41_fam.
DR InterPro; IPR011174; ERM.
DR InterPro; IPR011259; ERM_C_dom.
DR InterPro; IPR000798; Ez/rad/moesin_like.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
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.
DR InterPro; IPR011993; PH_like_dom.
DR Pfam; PF00769; ERM; 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 SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF48678; SSF48678; 1.
DR PROSITE; PS00660; FERM_1; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell membrane; Cell projection;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Membrane; Phosphoprotein; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 577 Moesin.
FT /FTId=PRO_0000219416.
FT DOMAIN 2 295 FERM.
FT MOD_RES 79 79 N6-acetyllysine.
FT MOD_RES 116 116 Phosphotyrosine.
FT MOD_RES 139 139 N6-acetyllysine.
FT MOD_RES 558 558 Phosphothreonine; by ROCK2 and STK10.
FT MUTAGEN 556 556 Y->R: Impairs phosphorylation by STK10.
FT MUTAGEN 558 558 T->A: Abolishes phosphorylation by STK10.
FT MUTAGEN 558 558 T->D: Phosphomimetic mutant.
FT STRAND 5 11
FT STRAND 14 20
FT HELIX 26 37
FT HELIX 42 44
FT STRAND 45 51
FT STRAND 56 58
FT STRAND 61 64
FT HELIX 65 67
FT STRAND 74 84
FT HELIX 89 92
FT HELIX 96 111
FT HELIX 119 134
FT TURN 139 141
FT TURN 144 149
FT HELIX 155 160
FT HELIX 165 178
FT TURN 179 181
FT HELIX 184 195
FT TURN 199 202
FT STRAND 204 209
FT STRAND 215 221
FT STRAND 224 229
FT STRAND 233 235
FT STRAND 237 241
FT HELIX 242 244
FT STRAND 245 251
FT STRAND 254 264
FT STRAND 267 270
FT HELIX 274 295
FT HELIX 301 343
FT HELIX 504 507
FT HELIX 511 514
FT HELIX 516 530
FT HELIX 540 550
FT HELIX 555 562
FT HELIX 567 575
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
//
ID MOES_HUMAN Reviewed; 577 AA.
AC P26038;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Moesin;
DE AltName: Full=Membrane-organizing extension spike protein;
GN Name=MSN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA 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.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA 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.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA 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.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA 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.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., 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
RT project: 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.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [5]
RP INTERACTION WITH SLC9A3R1.
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
RT associates with members of the ezrin-radixin-moesin family.";
RL J. Cell Biol. 139:169-179(1997).
RN [6]
RP INTERACTION WITH SELPLG AND SYK.
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
RT the leukocyte adhesion receptor PSGL-1.";
RL Immunity 17:401-412(2002).
RN [7]
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.,
RA Olah G., Verin A.D.;
RT "TIMAP is a positive regulator of pulmonary endothelial barrier
RT function.";
RL Am. J. Physiol. 295:L440-L450(2008).
RN [8]
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 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-116, AND MASS
RP SPECTROMETRY.
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-79 AND LYS-139, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [12]
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.,
RA Buerckstuemmer T., 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 [13]
RP FUNCTION, AND INTERACTION WITH MSN.
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.,
RA Walsh D., Naghavi M.H.;
RT "PDZD8 is a novel moesin-interacting cytoskeletal regulatory protein
RT that suppresses infection by herpes simplex virus type 1.";
RL Virology 415:114-121(2011).
RN [14]
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
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
RT masked by an extended actin binding tail domain.";
RL Cell 101:259-270(2000).
RN [16]
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:
RT an analysis of structural changes on activation.";
RL Biochemistry 40:7061-7068(2001).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 1-297 IN COMPLEX WITH
RP SLC9A3R1.
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
RT direct masking on the FERM domain.";
RL J. Cell Sci. 117:1547-1552(2004).
CC -!- FUNCTION: Probably involved in connections of major cytoskeletal
CC structures to the plasma membrane. May inhibit herpes simplex
CC virus 1 infection at an early stage.
CC -!- ENZYME REGULATION: A head-to-tail association, of the N-terminal
CC and C-terminal halves results in a closed conformation (inactive
CC form) which is incapable of actin or membrane-binding (By
CC similarity).
CC -!- SUBUNIT: In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex
CC which is disrupted upon TCR activation (By similarity). Binds
CC SLC9A3R1. Interacts with PPP1R16B. Interacts with PDZD8. Interacts
CC with SELPLG and SYK; mediates the activation of SYK by SELPLG.
CC -!- INTERACTION:
CC Q5S007:LRRK2; NbExp=5; IntAct=EBI-528768, EBI-5323863;
CC O14745:SLC9A3R1; NbExp=5; IntAct=EBI-528768, EBI-349787;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side (By similarity). Cytoplasm, cytoskeleton (By
CC similarity). Apical cell membrane; Peripheral membrane protein;
CC Cytoplasmic side (By similarity). Cell projection, microvillus
CC membrane; Peripheral membrane protein; Cytoplasmic side (By
CC similarity). Note=Phosphorylated form is enriched in microvilli-
CC like structures at apical membrane (By similarity). Increased cell
CC membrane localization of both phosphorylated and non-
CC phosphorylated forms seen after thrombin treatment.
CC -!- TISSUE SPECIFICITY: In all tissues and cultured cells studied.
CC -!- PTM: Phosphorylation on Thr-558 is crucial for the formation of
CC microvilli-like structures. Phosphorylation by ROCK2 suppresses
CC the head-to-tail association of the N-terminal and C-terminal
CC halves resulting in an opened conformation which is capable of
CC actin and membrane-binding (By similarity). Phosphorylation on
CC Thr-558 by STK10 negatively regulates lymphocyte migration and
CC polarization.
CC -!- SIMILARITY: Contains 1 FERM domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MSNID363.html";
CC -----------------------------------------------------------------------
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DR EMBL; M69066; AAA36322.1; -; mRNA.
DR EMBL; Z98946; CAB46379.1; -; Genomic_DNA.
DR EMBL; BC017293; AAH17293.1; -; mRNA.
DR PIR; A41289; A41289.
DR RefSeq; NP_002435.1; NM_002444.2.
DR UniGene; Hs.87752; -.
DR PDB; 1E5W; X-ray; 2.70 A; A=1-346.
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 PDBsum; 1E5W; -.
DR PDBsum; 1EF1; -.
DR PDBsum; 1SGH; -.
DR ProteinModelPortal; P26038; -.
DR SMR; P26038; 1-577.
DR IntAct; P26038; 13.
DR MINT; MINT-3010439; -.
DR STRING; 9606.ENSP00000353408; -.
DR PhosphoSite; P26038; -.
DR DMDM; 127234; -.
DR OGP; P26038; -.
DR PaxDb; P26038; -.
DR PeptideAtlas; P26038; -.
DR PRIDE; P26038; -.
DR DNASU; 4478; -.
DR Ensembl; ENST00000360270; ENSP00000353408; ENSG00000147065.
DR GeneID; 4478; -.
DR KEGG; hsa:4478; -.
DR UCSC; uc004dwf.3; human.
DR CTD; 4478; -.
DR GeneCards; GC0XP064887; -.
DR HGNC; HGNC:7373; MSN.
DR HPA; CAB010898; -.
DR HPA; CAB047338; -.
DR HPA; HPA000263; -.
DR HPA; HPA000763; -.
DR HPA; HPA011135; -.
DR HPA; HPA011227; -.
DR MIM; 309845; gene.
DR neXtProt; NX_P26038; -.
DR PharmGKB; PA31178; -.
DR eggNOG; NOG236035; -.
DR HOGENOM; HOG000007113; -.
DR HOVERGEN; HBG002185; -.
DR InParanoid; P26038; -.
DR KO; K05763; -.
DR OMA; PHVTEPM; -.
DR OrthoDB; EOG7BGHK6; -.
DR PhylomeDB; P26038; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; MSN; human.
DR EvolutionaryTrace; P26038; -.
DR GeneWiki; Moesin; -.
DR GenomeRNAi; 4478; -.
DR NextBio; 17331; -.
DR PMAP-CutDB; P26038; -.
DR PRO; PR:P26038; -.
DR Bgee; P26038; -.
DR CleanEx; HS_MSN; -.
DR Genevestigator; P26038; -.
DR GO; GO:0045177; C:apical part of cell; IDA:BHF-UCL.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic to membrane; IEA:InterPro.
DR GO; GO:0030175; C:filopodium; IDA:BHF-UCL.
DR GO; GO:0005902; C:microvillus; IDA:BHF-UCL.
DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001931; C:uropod; IEA:Ensembl.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
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:2000401; P:regulation of lymphocyte migration; IMP:UniProtKB.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR019750; Band_41_fam.
DR InterPro; IPR011174; ERM.
DR InterPro; IPR011259; ERM_C_dom.
DR InterPro; IPR000798; Ez/rad/moesin_like.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
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.
DR InterPro; IPR011993; PH_like_dom.
DR Pfam; PF00769; ERM; 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 SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF48678; SSF48678; 1.
DR PROSITE; PS00660; FERM_1; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell membrane; Cell projection;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Membrane; Phosphoprotein; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 577 Moesin.
FT /FTId=PRO_0000219416.
FT DOMAIN 2 295 FERM.
FT MOD_RES 79 79 N6-acetyllysine.
FT MOD_RES 116 116 Phosphotyrosine.
FT MOD_RES 139 139 N6-acetyllysine.
FT MOD_RES 558 558 Phosphothreonine; by ROCK2 and STK10.
FT MUTAGEN 556 556 Y->R: Impairs phosphorylation by STK10.
FT MUTAGEN 558 558 T->A: Abolishes phosphorylation by STK10.
FT MUTAGEN 558 558 T->D: Phosphomimetic mutant.
FT STRAND 5 11
FT STRAND 14 20
FT HELIX 26 37
FT HELIX 42 44
FT STRAND 45 51
FT STRAND 56 58
FT STRAND 61 64
FT HELIX 65 67
FT STRAND 74 84
FT HELIX 89 92
FT HELIX 96 111
FT HELIX 119 134
FT TURN 139 141
FT TURN 144 149
FT HELIX 155 160
FT HELIX 165 178
FT TURN 179 181
FT HELIX 184 195
FT TURN 199 202
FT STRAND 204 209
FT STRAND 215 221
FT STRAND 224 229
FT STRAND 233 235
FT STRAND 237 241
FT HELIX 242 244
FT STRAND 245 251
FT STRAND 254 264
FT STRAND 267 270
FT HELIX 274 295
FT HELIX 301 343
FT HELIX 504 507
FT HELIX 511 514
FT HELIX 516 530
FT HELIX 540 550
FT HELIX 555 562
FT HELIX 567 575
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
//
MIM
309845
*RECORD*
*FIELD* NO
309845
*FIELD* TI
*309845 MOESIN; MSN
;;MEMBRANE-ORGANIZING EXTENSION SPIKE PROTEIN
*FIELD* TX
CLONING
read more
Lankes et al. (1988) isolated from bovine uterus a protein that is a
candidate receptor for heparin or heparan sulfate in the interaction of
basement membrane heparan sulfate and cells. They called the protein
moesin (for membrane-organizing extension spike protein). Further
studies indicated a significant homology in sequence to ezrin (123900),
protein 4.1 (130500), talin (186745), radixin (179410), and merlin
(607379). These proteins constitute a family with structural and
probably functional relationships; all of them are localized to the
submembranous cytoskeleton. Moesin is widely expressed in different
tissues in cells, where it is localized to filopodia and other
membranous protrusions that are important for cell-cell recognition and
signaling and for cell movement.
Lankes and Furthmayr (1991) cloned and sequenced the complete cDNA of
moesin, which represents a single 4.2-kb mRNA encoding a protein of 577
amino acids. It contains no apparent signal peptide or transmembrane
domain.
GENE FUNCTION
The immunologic synapse is the T cell-APC (antigen-presenting cell)
contact site where T-cell receptors (TCRs), coreceptors, signaling
molecules, and adhesion receptors polarize upon antigen recognition. The
formation of the immunologic synapse is thought to be important for
receptor signal transduction and full T-lymphocyte activation. CD43
(182160) is a large sialoprotein diffusely expressed in unactivated T
cells. Using antigen-activated T cells and confocal microscopy, Delon et
al. (2001) demonstrated that moesin is excluded from the region of T
cell-APC contact and colocalizes with CD43. Western blot and
immunocytochemical analyses showed that moesin is rapidly
dephosphorylated upon antigen recognition and then rephosphorylated on
threonine residues. Only phosphorylated moesin was able to bind CD43.
Delon et al. (2001) concluded that T-cell activation requires the
removal of CD43 from the immunologic synapse to allow efficient
engagement of the TCR with molecules on the APC.
Using mouse helper T cell lines and confocal microscopy, Allenspach et
al. (2001) determined that the cytoplasmic tail of CD43 is necessary and
sufficient for CD43 removal from the immunologic synapse. In at least
some cells, CD43 is located at the distal pole of the T cell together
with ezrin and moesin. No differences in the behavior of ezrin and
moesin were noted throughout the study. Using cells from Cd43 -/- mice,
Allenspach et al. (2001) observed that ezrin-radixin-moesin (ERM) family
proteins move independently of the large CD43 mucin. Overexpression of a
dominant-negative ERM mutant containing the N-terminal 320 amino acids
of ezrin inhibited the activation-induced movement of CD43 without
affecting conjugate formation. The dominant-negative mutant reduced
cytokine production but not the expression of T-cell activation markers.
Speck et al. (2003) showed that the sole Drosophila ERM protein moesin
promotes cortical actin assembly and apical-basal polarity. As a result,
cells lacking moesin lose epithelial characteristics and adopt invasive
migratory behavior. Speck et al. (2003) concluded that moesin
facilitates epithelial morphology not by providing an essential
structural function, but rather by antagonizing activity of the small
GTPase Rho (RHOA; 165390). Thus, moesin functions in maintaining
epithelial integrity by regulating cell-signaling events that affect
actin organization and polarity. Furthermore, Speck et al. (2003)
demonstrated negative feedback between ERM activation and activity of
the Rho pathway.
Using antigen-activated T cells, Faure et al. (2004) showed that the ERM
proteins are rapidly inactivated through a VAV1 (164875)-RAC1 (602048)
pathway. The resulting disanchoring of the cortical actin cytoskeleton
from the plasma membrane decreased cellular rigidity, leading to more
efficient T cell-APC conjugate formation. The authors concluded that
this pathway favors immunologic synapse formation and the development of
an effective immune response.
By yeast 2-hybrid screening and coimmunoprecipitation analysis, Henning
et al. (2011) found that amino acids 990 to 1155 of human PDZD8 (614235)
interacted with amino acids 158 to 279 of moesin. Expression of PDZD8 or
moesin reduced the levels of stable microtubules in the human CHME3
microglial cell line. In addition, expression of PDZD8 or moesin reduced
the cytopathic effects of herpes simplex virus (HSV)-1, as well as HSV-1
replication and spread, in CHME3 cells.
Neisch et al. (2013) found that Drosophila conundrum (Conu), an ortholog
of human ARHGAP18 (613351), preferentially localized to apical cortex in
Drosophila epithelium and immunoprecipitated with moesin from S2
Drosophila epithelial cells. Moesin recruited Conu to the cell cortex,
and cortical Conu functioned as a GAP for Rho1, an ortholog of RHOA,
inhibiting Rho1 activity. Coexpression of moesin and Conu led to
overgrowth and convoluted folding of epithelium in vivo. Conu also
induced overproliferation by synergistically functioning with the small
GTPase Arf6 (600464) to promote activation of Rac1. Neisch et al. (2013)
concluded that moesin regulates epithelial growth by recruiting Conu to
the cell cortex, resulting in Rho1 inhibition and Rac1 activation.
GENE STRUCTURE
Wilgenbus et al. (1994) found that the human moesin gene has 12 exons
distributed over more than 30 kb.
MAPPING
By Southern and Western blot analyses of Chinese hamster/human somatic
cell hybrids and by fluorescence chromosomal in situ hybridization,
Wilgenbus et al. (1994) localized the MSN gene to Xq11.2-q12.
Moesin-like sequences were identified also on chromosomes 5 and 6. The
murine Msn locus was similarly mapped to the X chromosome by study of a
rodent/mouse hybrid panel.
PATHOGENESIS
Shcherbina et al. (1999) demonstrated a decrease in platelet moesin in
patients with Wiskott-Aldrich syndrome (301000). This appeared to be a
secondary defect to the primary defect in the WASP gene. The WASP and
MSN genes are both located on the X chromosome, on the short and the
long arm, respectively.
*FIELD* RF
1. Allenspach, E. J.; Cullinan, P.; Tong, J.; Tang, Q.; Tesciuba,
A. G.; Cannon, J. L.; Takahashi, S. M.; Morgan, R.; Burkhardt, J.
K.; Sperling, A. I.: ERM-dependent movement of CD43 defines a novel
protein complex distal to the immunological synapse. Immunity 15:
739-750, 2001.
2. Delon, J.; Kaibuchi, K.; Germain, R. N.: Exclusion of CD43 from
the immunological synapse is mediated by phosphorylation-regulated
relocation of the cytoskeletal adaptor moesin. Immunity 15: 691-701,
2001.
3. Faure, S.; Salazar-Fontana, L. I.; Semichon, M.; Tybulewicz, V.
L. J.; Bismuth, G.; Trautmann, A.; Germain, R. N.; Delon, J.: ERM
proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nature
Immun. 5: 272-279, 2004.
4. Henning, M. S.; Stiedl, P.; Barry, D. S.; McMahon, R.; Morham,
S. G.; Walsh, D.; Naghavi, M. H.: PDZD8 is a novel moesin-interacting
cytoskeletal regulatory protein that suppresses infection by herpes
simplex virus type 1. Virology 415: 114-121, 2011.
5. Lankes, W.; Griesmacher, A.; Grunwald, J.; Schwartz-Albiez, R.;
Keller, R.: A heparin-binding protein involved in inhibition of smooth-muscle
cell proliferation. Biochem. J. 251: 831-842, 1988.
6. Lankes, W. T.; Furthmayr, H.: Moesin: a member of the protein
4.1-talin-ezrin family of proteins. Proc. Nat. Acad. Sci. 88: 8297-8301,
1991.
7. Neisch, A. L.; Formstecher, E.; Fehon, R. G.: Conundrum, an ARHGAP18
orthologue, regulates RhoA and proliferation through interactions
with moesin. Molec. Biol. Cell 24: 1420-1433, 2013.
8. Shcherbina, A.; Bretscher, A.; Rosen, F. S.; Kenney, D. M.; Remold-O'Donnell,
E.: The cytoskeletal linker protein moesin: decreased levels in Wiskott-Aldrich
syndrome platelets and identification of a cleavage pathway in normal
platelets. Brit. J. Haemat. 106: 216-223, 1999. Note: Erratum: Brit.
J. Haemat. 107: 218 only, 1999.
9. Speck, O.; Hughes, S. C.; Noren, N. K.; Kulikauskas, R. M.; Fehon,
R. G.: Moesin functions antagonistically to the Rho pathway to maintain
epithelial integrity. Nature 421: 83-87, 2003.
10. Wilgenbus, K. K.; Hsieh, C.-L.; Lankes, W. T.; Milatovich, A.;
Francke, U.; Furthmayr, H.: Structure and localization on the X chromosome
of the gene coding for the human filopodial protein moesin (MSN). Genomics 19:
326-333, 1994.
*FIELD* CN
Patricia A. Hartz - updated: 11/25/2013
Paul J. Converse - updated: 9/20/2011
Paul J. Converse - updated: 2/13/2004
Ada Hamosh - updated: 2/3/2003
Paul J. Converse - updated: 2/8/2002
Victor A. McKusick - updated: 10/28/1999
*FIELD* CD
Victor A. McKusick: 4/27/1994
*FIELD* ED
mgross: 11/26/2013
mcolton: 11/25/2013
terry: 3/28/2013
mgross: 9/20/2011
alopez: 3/1/2004
mgross: 2/13/2004
alopez: 2/4/2003
terry: 2/3/2003
carol: 1/28/2003
mgross: 2/8/2002
mgross: 10/28/1999
carol: 4/27/1994
*RECORD*
*FIELD* NO
309845
*FIELD* TI
*309845 MOESIN; MSN
;;MEMBRANE-ORGANIZING EXTENSION SPIKE PROTEIN
*FIELD* TX
CLONING
read more
Lankes et al. (1988) isolated from bovine uterus a protein that is a
candidate receptor for heparin or heparan sulfate in the interaction of
basement membrane heparan sulfate and cells. They called the protein
moesin (for membrane-organizing extension spike protein). Further
studies indicated a significant homology in sequence to ezrin (123900),
protein 4.1 (130500), talin (186745), radixin (179410), and merlin
(607379). These proteins constitute a family with structural and
probably functional relationships; all of them are localized to the
submembranous cytoskeleton. Moesin is widely expressed in different
tissues in cells, where it is localized to filopodia and other
membranous protrusions that are important for cell-cell recognition and
signaling and for cell movement.
Lankes and Furthmayr (1991) cloned and sequenced the complete cDNA of
moesin, which represents a single 4.2-kb mRNA encoding a protein of 577
amino acids. It contains no apparent signal peptide or transmembrane
domain.
GENE FUNCTION
The immunologic synapse is the T cell-APC (antigen-presenting cell)
contact site where T-cell receptors (TCRs), coreceptors, signaling
molecules, and adhesion receptors polarize upon antigen recognition. The
formation of the immunologic synapse is thought to be important for
receptor signal transduction and full T-lymphocyte activation. CD43
(182160) is a large sialoprotein diffusely expressed in unactivated T
cells. Using antigen-activated T cells and confocal microscopy, Delon et
al. (2001) demonstrated that moesin is excluded from the region of T
cell-APC contact and colocalizes with CD43. Western blot and
immunocytochemical analyses showed that moesin is rapidly
dephosphorylated upon antigen recognition and then rephosphorylated on
threonine residues. Only phosphorylated moesin was able to bind CD43.
Delon et al. (2001) concluded that T-cell activation requires the
removal of CD43 from the immunologic synapse to allow efficient
engagement of the TCR with molecules on the APC.
Using mouse helper T cell lines and confocal microscopy, Allenspach et
al. (2001) determined that the cytoplasmic tail of CD43 is necessary and
sufficient for CD43 removal from the immunologic synapse. In at least
some cells, CD43 is located at the distal pole of the T cell together
with ezrin and moesin. No differences in the behavior of ezrin and
moesin were noted throughout the study. Using cells from Cd43 -/- mice,
Allenspach et al. (2001) observed that ezrin-radixin-moesin (ERM) family
proteins move independently of the large CD43 mucin. Overexpression of a
dominant-negative ERM mutant containing the N-terminal 320 amino acids
of ezrin inhibited the activation-induced movement of CD43 without
affecting conjugate formation. The dominant-negative mutant reduced
cytokine production but not the expression of T-cell activation markers.
Speck et al. (2003) showed that the sole Drosophila ERM protein moesin
promotes cortical actin assembly and apical-basal polarity. As a result,
cells lacking moesin lose epithelial characteristics and adopt invasive
migratory behavior. Speck et al. (2003) concluded that moesin
facilitates epithelial morphology not by providing an essential
structural function, but rather by antagonizing activity of the small
GTPase Rho (RHOA; 165390). Thus, moesin functions in maintaining
epithelial integrity by regulating cell-signaling events that affect
actin organization and polarity. Furthermore, Speck et al. (2003)
demonstrated negative feedback between ERM activation and activity of
the Rho pathway.
Using antigen-activated T cells, Faure et al. (2004) showed that the ERM
proteins are rapidly inactivated through a VAV1 (164875)-RAC1 (602048)
pathway. The resulting disanchoring of the cortical actin cytoskeleton
from the plasma membrane decreased cellular rigidity, leading to more
efficient T cell-APC conjugate formation. The authors concluded that
this pathway favors immunologic synapse formation and the development of
an effective immune response.
By yeast 2-hybrid screening and coimmunoprecipitation analysis, Henning
et al. (2011) found that amino acids 990 to 1155 of human PDZD8 (614235)
interacted with amino acids 158 to 279 of moesin. Expression of PDZD8 or
moesin reduced the levels of stable microtubules in the human CHME3
microglial cell line. In addition, expression of PDZD8 or moesin reduced
the cytopathic effects of herpes simplex virus (HSV)-1, as well as HSV-1
replication and spread, in CHME3 cells.
Neisch et al. (2013) found that Drosophila conundrum (Conu), an ortholog
of human ARHGAP18 (613351), preferentially localized to apical cortex in
Drosophila epithelium and immunoprecipitated with moesin from S2
Drosophila epithelial cells. Moesin recruited Conu to the cell cortex,
and cortical Conu functioned as a GAP for Rho1, an ortholog of RHOA,
inhibiting Rho1 activity. Coexpression of moesin and Conu led to
overgrowth and convoluted folding of epithelium in vivo. Conu also
induced overproliferation by synergistically functioning with the small
GTPase Arf6 (600464) to promote activation of Rac1. Neisch et al. (2013)
concluded that moesin regulates epithelial growth by recruiting Conu to
the cell cortex, resulting in Rho1 inhibition and Rac1 activation.
GENE STRUCTURE
Wilgenbus et al. (1994) found that the human moesin gene has 12 exons
distributed over more than 30 kb.
MAPPING
By Southern and Western blot analyses of Chinese hamster/human somatic
cell hybrids and by fluorescence chromosomal in situ hybridization,
Wilgenbus et al. (1994) localized the MSN gene to Xq11.2-q12.
Moesin-like sequences were identified also on chromosomes 5 and 6. The
murine Msn locus was similarly mapped to the X chromosome by study of a
rodent/mouse hybrid panel.
PATHOGENESIS
Shcherbina et al. (1999) demonstrated a decrease in platelet moesin in
patients with Wiskott-Aldrich syndrome (301000). This appeared to be a
secondary defect to the primary defect in the WASP gene. The WASP and
MSN genes are both located on the X chromosome, on the short and the
long arm, respectively.
*FIELD* RF
1. Allenspach, E. J.; Cullinan, P.; Tong, J.; Tang, Q.; Tesciuba,
A. G.; Cannon, J. L.; Takahashi, S. M.; Morgan, R.; Burkhardt, J.
K.; Sperling, A. I.: ERM-dependent movement of CD43 defines a novel
protein complex distal to the immunological synapse. Immunity 15:
739-750, 2001.
2. Delon, J.; Kaibuchi, K.; Germain, R. N.: Exclusion of CD43 from
the immunological synapse is mediated by phosphorylation-regulated
relocation of the cytoskeletal adaptor moesin. Immunity 15: 691-701,
2001.
3. Faure, S.; Salazar-Fontana, L. I.; Semichon, M.; Tybulewicz, V.
L. J.; Bismuth, G.; Trautmann, A.; Germain, R. N.; Delon, J.: ERM
proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nature
Immun. 5: 272-279, 2004.
4. Henning, M. S.; Stiedl, P.; Barry, D. S.; McMahon, R.; Morham,
S. G.; Walsh, D.; Naghavi, M. H.: PDZD8 is a novel moesin-interacting
cytoskeletal regulatory protein that suppresses infection by herpes
simplex virus type 1. Virology 415: 114-121, 2011.
5. Lankes, W.; Griesmacher, A.; Grunwald, J.; Schwartz-Albiez, R.;
Keller, R.: A heparin-binding protein involved in inhibition of smooth-muscle
cell proliferation. Biochem. J. 251: 831-842, 1988.
6. Lankes, W. T.; Furthmayr, H.: Moesin: a member of the protein
4.1-talin-ezrin family of proteins. Proc. Nat. Acad. Sci. 88: 8297-8301,
1991.
7. Neisch, A. L.; Formstecher, E.; Fehon, R. G.: Conundrum, an ARHGAP18
orthologue, regulates RhoA and proliferation through interactions
with moesin. Molec. Biol. Cell 24: 1420-1433, 2013.
8. Shcherbina, A.; Bretscher, A.; Rosen, F. S.; Kenney, D. M.; Remold-O'Donnell,
E.: The cytoskeletal linker protein moesin: decreased levels in Wiskott-Aldrich
syndrome platelets and identification of a cleavage pathway in normal
platelets. Brit. J. Haemat. 106: 216-223, 1999. Note: Erratum: Brit.
J. Haemat. 107: 218 only, 1999.
9. Speck, O.; Hughes, S. C.; Noren, N. K.; Kulikauskas, R. M.; Fehon,
R. G.: Moesin functions antagonistically to the Rho pathway to maintain
epithelial integrity. Nature 421: 83-87, 2003.
10. Wilgenbus, K. K.; Hsieh, C.-L.; Lankes, W. T.; Milatovich, A.;
Francke, U.; Furthmayr, H.: Structure and localization on the X chromosome
of the gene coding for the human filopodial protein moesin (MSN). Genomics 19:
326-333, 1994.
*FIELD* CN
Patricia A. Hartz - updated: 11/25/2013
Paul J. Converse - updated: 9/20/2011
Paul J. Converse - updated: 2/13/2004
Ada Hamosh - updated: 2/3/2003
Paul J. Converse - updated: 2/8/2002
Victor A. McKusick - updated: 10/28/1999
*FIELD* CD
Victor A. McKusick: 4/27/1994
*FIELD* ED
mgross: 11/26/2013
mcolton: 11/25/2013
terry: 3/28/2013
mgross: 9/20/2011
alopez: 3/1/2004
mgross: 2/13/2004
alopez: 2/4/2003
terry: 2/3/2003
carol: 1/28/2003
mgross: 2/8/2002
mgross: 10/28/1999
carol: 4/27/1994