EZRI_HUMAN
ID EZRI_HUMAN Reviewed; 586 AA.
AC P15311; E1P5A8; P23714; Q4VX75; Q96CU8; Q9NSJ4;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 4.
DT 03-AUG-2022, entry version 236.
DE RecName: Full=Ezrin;
DE AltName: Full=Cytovillin;
DE AltName: Full=Villin-2;
DE AltName: Full=p81;
GN Name=EZR; Synonyms=VIL2;
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], PARTIAL PROTEIN SEQUENCE, AND VARIANT VAL-532.
RX PubMed=2591371; DOI=10.1002/j.1460-2075.1989.tb08598.x;
RA Gould K.L., Bretscher A., Esch F.S., Hunter T.;
RT "cDNA cloning and sequencing of the protein-tyrosine kinase substrate,
RT ezrin, reveals homology to band 4.1.";
RL EMBO J. 8:4133-4142(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-532.
RC TISSUE=Placenta;
RX PubMed=2674140; DOI=10.1016/s0021-9258(19)84765-8;
RA Turunen O., Winqvist R., Pakkanen R., Grzeschik K.-H., Wahlstroem T.,
RA Vaheri A.;
RT "Cytovillin, a microvillar Mr 75,000 protein. cDNA sequence, prokaryotic
RT expression, and chromosomal localization.";
RL J. Biol. Chem. 264:16727-16732(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 172-180 AND 343-350.
RX PubMed=8713105; DOI=10.1006/bbrc.1996.1082;
RA Egerton M., Moritz R.L., Druker B., Kelso A., Simpson R.J.;
RT "Identification of the 70kD heat shock cognate protein (Hsc70) and alpha-
RT actinin-1 as novel phosphotyrosine-containing proteins in T lymphocytes.";
RL Biochem. Biophys. Res. Commun. 224:666-674(1996).
RN [8]
RP PROTEIN SEQUENCE OF 264-273; 428-435 AND 530-542, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP PHOSPHORYLATION AT TYR-146 AND TYR-354 BY PDGFR.
RX PubMed=1382070; DOI=10.1016/s0021-9258(18)41769-3;
RA Krieg J., Hunter T.;
RT "Identification of the two major epidermal growth factor-induced tyrosine
RT phosphorylation sites in the microvillar core protein ezrin.";
RL J. Biol. Chem. 267:19258-19265(1992).
RN [10]
RP PHOSPHORYLATION.
RX PubMed=1381389;
RA Egerton M., Burgess W.H., Chen D., Druker B.J., Bretscher A.,
RA Samelson L.E.;
RT "Identification of ezrin as an 81-kDa tyrosine-phosphorylated protein in T
RT cells.";
RL J. Immunol. 149:1847-1852(1992).
RN [11]
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 associates
RT with members of the ezrin-radixin-moesin family.";
RL J. Cell Biol. 139:169-179(1997).
RN [12]
RP INTERACTION WITH SCYL3.
RC TISSUE=Kidney;
RX PubMed=12651155; DOI=10.1016/s0014-4827(02)00054-x;
RA Sullivan A., Uff C.R., Isacke C.M., Thorne R.F.;
RT "PACE-1, a novel protein that interacts with the C-terminal domain of
RT ezrin.";
RL Exp. Cell Res. 284:224-238(2003).
RN [13]
RP INTERACTION WITH S100P.
RX PubMed=12808036; DOI=10.1091/mbc.e02-09-0553;
RA Koltzscher M., Neumann C., Konig S., Gerke V.;
RT "Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P.";
RL Mol. Biol. Cell 14:2372-2384(2003).
RN [14]
RP INTERACTION WITH TMEM8B.
RX PubMed=15498789; DOI=10.1093/carcin/bgh312;
RA Ma J., Zhou J., Fan S., Wang L.-L., Li X.-L., Yan Q., Zhou M., Liu H.-Y.,
RA Zhang Q., Zhou H., Gan K., Li Z., Peng C., Xiong W., Tan C., Shen S.-R.,
RA Yang J., Li J., Li G.-Y.;
RT "Role of a novel EGF-like domain-containing gene NGX6 in cell adhesion
RT modulation in nasopharyngeal carcinoma cells.";
RL Carcinogenesis 26:281-291(2005).
RN [15]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15797715; DOI=10.1016/j.mcn.2004.11.014;
RA Groenholm M., Teesalu T., Tyynelaa J., Piltti K., Boehling T.,
RA Wartiovaara K., Vaheri A., Carpen O.;
RT "Characterization of the NF2 protein merlin and the ERM protein ezrin in
RT human, rat, and mouse central nervous system.";
RL Mol. Cell. Neurosci. 28:683-693(2005).
RN [16]
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 [17]
RP INTERACTION WITH PODXL.
RX PubMed=17616675; DOI=10.1158/0008-5472.can-06-3575;
RA Sizemore S., Cicek M., Sizemore N., Ng K.P., Casey G.;
RT "Podocalyxin increases the aggressive phenotype of breast and prostate
RT cancer cells in vitro through its interaction with ezrin.";
RL Cancer Res. 67:6183-6191(2007).
RN [18]
RP FUNCTION, AND INTERACTION WITH PLEKHG6.
RX PubMed=17881735; DOI=10.1091/mbc.e06-12-1144;
RA D'Angelo R., Aresta S., Blangy A., Del Maestro L., Louvard D., Arpin M.;
RT "Interaction of ezrin with the novel guanine nucleotide exchange factor
RT PLEKHG6 promotes RhoG-dependent apical cytoskeleton rearrangements in
RT epithelial cells.";
RL Mol. Biol. Cell 18:4780-4793(2007).
RN [19]
RP INTERACTION WITH FES/FPS, PHOSPHORYLATION AT TYR-146 AND TYR-478, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18046454; DOI=10.1038/sj.emboj.7601943;
RA Naba A., Reverdy C., Louvard D., Arpin M.;
RT "Spatial recruitment and activation of the Fes kinase by ezrin promotes
RT HGF-induced cell scattering.";
RL EMBO J. 27:38-50(2008).
RN [20]
RP FUNCTION, AND PHOSPHORYLATION AT THR-567.
RX PubMed=18270268; DOI=10.1242/jcs.016246;
RA Wald F.A., Oriolo A.S., Mashukova A., Fregien N.L., Langshaw A.H.,
RA Salas P.J.;
RT "Atypical protein kinase C (iota) activates ezrin in the apical domain of
RT intestinal epithelial cells.";
RL J. Cell Sci. 121:644-654(2008).
RN [21]
RP FUNCTION, AND INTERACTION WITH S100P.
RX PubMed=19111582; DOI=10.1016/j.bbamcr.2008.11.012;
RA Austermann J., Nazmi A.R., Heil A., Fritz G., Kolinski M., Filipek S.,
RA Gerke V.;
RT "Generation and characterization of a novel, permanently active S100P
RT mutant.";
RL Biochim. Biophys. Acta 1793:1078-1085(2009).
RN [22]
RP INTERACTION WITH MCC.
RX PubMed=19555689; DOI=10.1016/j.febslet.2009.06.034;
RA Arnaud C., Sebbagh M., Nola S., Audebert S., Bidaut G., Hermant A.,
RA Gayet O., Dusetti N.J., Ollendorff V., Santoni M.J., Borg J.P., Lecine P.;
RT "MCC, a new interacting protein for Scrib, is required for cell migration
RT in epithelial cells.";
RL FEBS Lett. 583:2326-2332(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-60, AND IDENTIFICATION BY MASS
RP 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 [24]
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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-366, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP S-NITROSYLATION, 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 [27]
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 [28]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-297.
RX PubMed=12429733; DOI=10.1074/jbc.m210601200;
RA Smith W.J., Nassar N., Bretscher A., Cerione R.A., Karplus P.A.;
RT "Structure of the active N-terminal domain of Ezrin. Conformational and
RT mobility changes identify keystone interactions.";
RL J. Biol. Chem. 278:4949-4956(2003).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-296, DOMAIN, AND SUBUNIT.
RX PubMed=27364155; DOI=10.1042/bcj20160541;
RA Phang J.M., Harrop S.J., Duff A.P., Sokolova A.V., Crossett B., Walsh J.C.,
RA Beckham S.A., Nguyen C.D., Davies R.B., Glockner C., Bromley E.H.,
RA Wilk K.E., Curmi P.M.;
RT "Structural characterization suggests models for monomeric and dimeric
RT forms of full-length ezrin.";
RL Biochem. J. 473:2763-2782(2016).
CC -!- FUNCTION: Probably involved in connections of major cytoskeletal
CC structures to the plasma membrane. In epithelial cells, required for
CC the formation of microvilli and membrane ruffles on the apical pole.
CC Along with PLEKHG6, required for normal macropinocytosis.
CC {ECO:0000269|PubMed:17881735, ECO:0000269|PubMed:18270268,
CC ECO:0000269|PubMed:19111582}.
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. {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Homodimer (PubMed:27364155). Interacts with PALS1 and
CC SLC9A3R2. Found in a complex with EZR, PODXL and SLC9A3R2 (By
CC similarity). Interacts with MCC, PLEKHG6, PODXL, SCYL3/PACE1, SLC9A3R1
CC and TMEM8B (PubMed:9314537, PubMed:12651155, PubMed:15498789,
CC PubMed:17616675, PubMed:17881735, PubMed:19555689). Interacts (when
CC phosphorylated) with FES/FPS (PubMed:18046454). Interacts with dimeric
CC S100P, the interaction may be activating through unmasking of F-actin
CC binding sites (PubMed:12808036, PubMed:19111582). Identified in
CC complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX
CC and spectrin (By similarity). Detected in a complex composed of at
CC least EZR, AHNAK, PPL and PRX (By similarity). Interacts with PDPN (via
CC cytoplasmic domain); activates RHOA and promotes epithelial-mesenchymal
CC transition (PubMed:17046996). Interacts with SPN/CD43 cytoplasmic tail,
CC CD44 and ICAM2 (By similarity). {ECO:0000250|UniProtKB:P26040,
CC ECO:0000250|UniProtKB:P31976, ECO:0000250|UniProtKB:P31977,
CC ECO:0000250|UniProtKB:Q8HZQ5, ECO:0000269|PubMed:12651155,
CC ECO:0000269|PubMed:12808036, ECO:0000269|PubMed:15498789,
CC ECO:0000269|PubMed:17046996, ECO:0000269|PubMed:17616675,
CC ECO:0000269|PubMed:17881735, ECO:0000269|PubMed:18046454,
CC ECO:0000269|PubMed:19111582, ECO:0000269|PubMed:19555689,
CC ECO:0000269|PubMed:27364155, ECO:0000269|PubMed:9314537}.
CC -!- INTERACTION:
CC P15311; Q14457: BECN1; NbExp=3; IntAct=EBI-1056902, EBI-949378;
CC P15311; Q8WU43: C2orf15; NbExp=3; IntAct=EBI-1056902, EBI-12904676;
CC P15311; P07384: CAPN1; NbExp=2; IntAct=EBI-1056902, EBI-1542113;
CC P15311; P15311: EZR; NbExp=7; IntAct=EBI-1056902, EBI-1056902;
CC P15311; P07332: FES; NbExp=8; IntAct=EBI-1056902, EBI-1055635;
CC P15311; P42858: HTT; NbExp=4; IntAct=EBI-1056902, EBI-466029;
CC P15311; Q8IZU9: KIRREL3; NbExp=5; IntAct=EBI-1056902, EBI-16427312;
CC P15311; Q00987: MDM2; NbExp=3; IntAct=EBI-1056902, EBI-389668;
CC P15311; Q8N108-16: MIER1; NbExp=3; IntAct=EBI-1056902, EBI-25830642;
CC P15311; Q8IVT2: MISP; NbExp=4; IntAct=EBI-1056902, EBI-2555085;
CC P15311; P35241: RDX; NbExp=6; IntAct=EBI-1056902, EBI-2514878;
CC P15311; P29034: S100A2; NbExp=2; IntAct=EBI-1056902, EBI-752230;
CC P15311; P26447: S100A4; NbExp=3; IntAct=EBI-1056902, EBI-717058;
CC P15311; Q8IZE3: SCYL3; NbExp=5; IntAct=EBI-1056902, EBI-1380680;
CC P15311; P55011: SLC12A2; NbExp=3; IntAct=EBI-1056902, EBI-2801449;
CC P15311; O14745: SLC9A3R1; NbExp=6; IntAct=EBI-1056902, EBI-349787;
CC P15311; Q8WTV1: THAP3; NbExp=3; IntAct=EBI-1056902, EBI-17438286;
CC P15311; Q63155: Dcc; Xeno; NbExp=3; IntAct=EBI-1056902, EBI-1798965;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:18046454}; Peripheral membrane protein
CC {ECO:0000269|PubMed:18046454}; Cytoplasmic side
CC {ECO:0000269|PubMed:18046454}. Cell projection
CC {ECO:0000269|PubMed:18046454}. Cell projection, microvillus membrane
CC {ECO:0000269|PubMed:18046454}; Peripheral membrane protein
CC {ECO:0000269|PubMed:18046454}; Cytoplasmic side
CC {ECO:0000269|PubMed:18046454}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:18046454}; Peripheral membrane protein
CC {ECO:0000269|PubMed:18046454}; Cytoplasmic side
CC {ECO:0000269|PubMed:18046454}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:18046454}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:18046454}. Cell projection, microvillus
CC {ECO:0000250|UniProtKB:P26040}. Note=Localization to the apical
CC membrane of parietal cells depends on the interaction with PALS1.
CC Localizes to cell extensions and peripheral processes of astrocytes (By
CC similarity). Microvillar peripheral membrane protein (cytoplasmic
CC side). {ECO:0000250|UniProtKB:P31977}.
CC -!- TISSUE SPECIFICITY: Expressed in cerebral cortex, basal ganglia,
CC hippocampus, hypophysis, and optic nerve. Weakly expressed in brain
CC stem and diencephalon. Stronger expression was detected in gray matter
CC of frontal lobe compared to white matter (at protein level). Component
CC of the microvilli of intestinal epithelial cells. Preferentially
CC expressed in astrocytes of hippocampus, frontal cortex, thalamus,
CC parahippocampal cortex, amygdala, insula, and corpus callosum. Not
CC detected in neurons in most tissues studied.
CC {ECO:0000269|PubMed:15797715}.
CC -!- DEVELOPMENTAL STAGE: Very strong staining is detected in the Purkinje
CC cell layer and in part of the molecular layer of the infant brain
CC compared to adult brain. {ECO:0000269|PubMed:15797715}.
CC -!- DOMAIN: Has three main structural domains: an N-terminal FERM domain, a
CC central alpha-helical domain and a C-terminal actin-binding domain.
CC {ECO:0000269|PubMed:27364155}.
CC -!- DOMAIN: The FERM domain is organized in a clover-shaped structure that
CC comprises three subdomains identified as F1 (residues 2-82), F2
CC (residues 96-198), and F3 (residues 204-296). In the active form, the
CC subdomain F3 adopts two mutually exclusive conformational isomers where
CC a row of four phenylalanine side chains (Phe250, Phe255, Phe267 and
CC Phe269) must point in the same direction. In the autoinhibited form,
CC the F3 subdomain interacts with the C-terminal domain (residues 516-
CC 586) and stabilizes the structure, selecting only one possible
CC arrangement of phenylalanine side chains. The FERM domain mediates
CC binding to membrane lipids and signaling molecules.
CC {ECO:0000269|PubMed:27364155}.
CC -!- DOMAIN: The central alpha-helical domain is composed of two alpha
CC helices (residues 326-406 and 417-466) connected by a linker. It
CC protrudes from the FERM domain forming a coiled coil structure where
CC the linker can have either a loop or a helix conformation. The monomer
CC is predicted to form an intra-molecular helix-loop-helix coiled coil
CC structure. Whereas the dimer adopts an elongated dumbbell-shaped
CC configuration where continuous alpha helices from each protomer are
CC organized in a antiparallel coiled coil structure that connect FERM:C-
CC terminal domain swapped complex at each end. The dimer is predicted to
CC link actin filaments parallel to the plasma membrane.
CC {ECO:0000305|PubMed:27364155}.
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: Phosphorylated by tyrosine-protein kinases. Phosphorylation by
CC ROCK2 suppresses the head-to-tail association of the N-terminal and C-
CC terminal halves resulting in an opened conformation which is capable of
CC actin and membrane-binding (By similarity). {ECO:0000250}.
CC -!- PTM: S-nitrosylation is induced by interferon-gamma and oxidatively-
CC modified low-densitity lipoprotein (LDL(ox)) possibly implicating the
CC iNOS-S100A8/9 transnitrosylase complex. {ECO:0000305|PubMed:25417112}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA61278.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB82418.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X51521; CAA35893.1; -; mRNA.
DR EMBL; J05021; AAA61278.1; ALT_INIT; mRNA.
DR EMBL; AL162086; CAB82418.1; ALT_INIT; mRNA.
DR EMBL; AL589931; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47647.1; -; Genomic_DNA.
DR EMBL; BC013903; AAH13903.1; -; mRNA.
DR CCDS; CCDS5258.1; -.
DR PIR; A34400; A34400.
DR RefSeq; NP_001104547.1; NM_001111077.1.
DR RefSeq; NP_003370.2; NM_003379.4.
DR PDB; 1NI2; X-ray; 2.30 A; A/B=2-297.
DR PDB; 4RM8; X-ray; 1.90 A; A/B=1-586.
DR PDB; 4RM9; X-ray; 2.00 A; A=1-586.
DR PDB; 4RMA; X-ray; 1.75 A; A/B=1-296.
DR PDBsum; 1NI2; -.
DR PDBsum; 4RM8; -.
DR PDBsum; 4RM9; -.
DR PDBsum; 4RMA; -.
DR AlphaFoldDB; P15311; -.
DR BMRB; P15311; -.
DR SMR; P15311; -.
DR BioGRID; 113271; 485.
DR CORUM; P15311; -.
DR DIP; DIP-38868N; -.
DR ELM; P15311; -.
DR IntAct; P15311; 249.
DR MINT; P15311; -.
DR STRING; 9606.ENSP00000356042; -.
DR BindingDB; P15311; -.
DR ChEMBL; CHEMBL1932896; -.
DR GlyGen; P15311; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P15311; -.
DR MetOSite; P15311; -.
DR PhosphoSitePlus; P15311; -.
DR SwissPalm; P15311; -.
DR BioMuta; EZR; -.
DR DMDM; 125987826; -.
DR DOSAC-COBS-2DPAGE; P15311; -.
DR REPRODUCTION-2DPAGE; IPI00843975; -.
DR SWISS-2DPAGE; P15311; -.
DR CPTAC; CPTAC-1398; -.
DR CPTAC; CPTAC-1399; -.
DR CPTAC; CPTAC-1400; -.
DR CPTAC; CPTAC-1401; -.
DR CPTAC; CPTAC-1402; -.
DR CPTAC; CPTAC-712; -.
DR EPD; P15311; -.
DR jPOST; P15311; -.
DR MassIVE; P15311; -.
DR MaxQB; P15311; -.
DR PaxDb; P15311; -.
DR PeptideAtlas; P15311; -.
DR PRIDE; P15311; -.
DR ProteomicsDB; 53128; -.
DR TopDownProteomics; P15311; -.
DR ABCD; P15311; 1 sequenced antibody.
DR Antibodypedia; 3417; 1513 antibodies from 46 providers.
DR CPTC; P15311; 2 antibodies.
DR DNASU; 7430; -.
DR Ensembl; ENST00000337147.11; ENSP00000338934.7; ENSG00000092820.19.
DR Ensembl; ENST00000367075.4; ENSP00000356042.3; ENSG00000092820.19.
DR GeneID; 7430; -.
DR KEGG; hsa:7430; -.
DR MANE-Select; ENST00000367075.4; ENSP00000356042.3; NM_001111077.2; NP_001104547.1.
DR UCSC; uc003qrt.5; human.
DR CTD; 7430; -.
DR DisGeNET; 7430; -.
DR GeneCards; EZR; -.
DR HGNC; HGNC:12691; EZR.
DR HPA; ENSG00000092820; Low tissue specificity.
DR MalaCards; EZR; -.
DR MIM; 123900; gene.
DR neXtProt; NX_P15311; -.
DR OpenTargets; ENSG00000092820; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA162385512; -.
DR VEuPathDB; HostDB:ENSG00000092820; -.
DR eggNOG; KOG3529; Eukaryota.
DR GeneTree; ENSGT00960000186596; -.
DR HOGENOM; CLU_003623_6_2_1; -.
DR InParanoid; P15311; -.
DR OMA; XVVKTIG; -.
DR OrthoDB; 627741at2759; -.
DR PhylomeDB; P15311; -.
DR TreeFam; TF313935; -.
DR PathwayCommons; P15311; -.
DR Reactome; R-HSA-373752; Netrin-1 signaling.
DR Reactome; R-HSA-437239; Recycling pathway of L1.
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 SignaLink; P15311; -.
DR SIGNOR; P15311; -.
DR BioGRID-ORCS; 7430; 21 hits in 1087 CRISPR screens.
DR ChiTaRS; EZR; human.
DR EvolutionaryTrace; P15311; -.
DR GeneWiki; Ezrin; -.
DR GenomeRNAi; 7430; -.
DR Pharos; P15311; Tbio.
DR PRO; PR:P15311; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P15311; protein.
DR Bgee; ENSG00000092820; Expressed in ventricular zone and 207 other tissues.
DR ExpressionAtlas; P15311; baseline and differential.
DR Genevisible; P15311; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005884; C:actin filament; IDA:HGNC-UCL.
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; ISS:UniProtKB.
DR GO; GO:0005903; C:brush border; ISS:UniProtKB.
DR GO; GO:0071944; C:cell periphery; IDA:UniProtKB.
DR GO; GO:0042995; C:cell projection; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IEA:Ensembl.
DR GO; GO:0030863; C:cortical cytoskeleton; TAS:HGNC-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0098592; C:cytoplasmic side of apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IDA:BHF-UCL.
DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0044853; C:plasma membrane raft; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001931; C:uropod; IEA:Ensembl.
DR GO; GO:0031982; C:vesicle; HDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; IPI:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:BHF-UCL.
DR GO; GO:0097718; F:disordered domain specific binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008017; F:microtubule binding; IMP:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0051018; F:protein kinase A binding; IPI:UniProtKB.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; IPI:UniProtKB.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0044548; F:S100 protein binding; IPI:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0051017; P:actin filament bundle assembly; IDA:UniProtKB.
DR GO; GO:0030953; P:astral microtubule organization; IMP:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IMP:UniProtKB.
DR GO; GO:0043622; P:cortical microtubule organization; IMP:UniProtKB.
DR GO; GO:0051660; P:establishment of centrosome localization; IMP:UniProtKB.
DR GO; GO:0061028; P:establishment of endothelial barrier; IGI:UniProtKB.
DR GO; GO:0035088; P:establishment or maintenance of apical/basal cell polarity; IEA:Ensembl.
DR GO; GO:0046847; P:filopodium assembly; IMP:UniProtKB.
DR GO; GO:0001951; P:intestinal D-glucose absorption; IEA:Ensembl.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IEP:BHF-UCL.
DR GO; GO:0022614; P:membrane to membrane docking; IEP:BHF-UCL.
DR GO; GO:0030033; P:microvillus assembly; IMP:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IMP:UniProtKB.
DR GO; GO:1903753; P:negative regulation of p38MAPK cascade; IMP:UniProtKB.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IDA:UniProtKB.
DR GO; GO:2000643; P:positive regulation of early endosome to late endosome transport; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:UniProtKB.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; 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:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0010737; P:protein kinase A signaling; IMP:UniProtKB.
DR GO; GO:0072697; P:protein localization to cell cortex; IMP:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0031503; P:protein-containing complex localization; IMP:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; IEA:Ensembl.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0032532; P:regulation of microvillus length; IEA:Ensembl.
DR GO; GO:1902115; P:regulation of organelle assembly; IMP:UniProtKB.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:1902896; P:terminal web assembly; IEA:Ensembl.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd13194; FERM_C_ERM; 1.
DR DisProt; DP00775; -.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 6.10.360.10; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR011174; ERM.
DR InterPro; IPR041789; ERM_FERM_C.
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; PTHR23281; 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; SSF47031; SSF47031; 1.
DR SUPFAM; SSF48678; SSF48678; 1.
DR SUPFAM; SSF54236; SSF54236; 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; Cell shape;
KW Coiled coil; Cytoplasm; Cytoskeleton; Direct protein sequencing; Membrane;
KW Phosphoprotein; Reference proteome; S-nitrosylation.
FT CHAIN 1..586
FT /note="Ezrin"
FT /id="PRO_0000219408"
FT DOMAIN 2..296
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT REGION 244..586
FT /note="Interaction with SCYL3"
FT /evidence="ECO:0000269|PubMed:12651155"
FT REGION 306..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..564
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 302..462
FT /evidence="ECO:0000255"
FT MOTIF 115..120
FT /note="[IL]-x-C-x-x-[DE] motif"
FT /evidence="ECO:0000305|PubMed:25417112"
FT COMPBIAS 505..527
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 540..564
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 60
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 146
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000269|PubMed:1382070,
FT ECO:0000269|PubMed:18046454"
FT MOD_RES 354
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000269|PubMed:1382070"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 478
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18046454"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26040"
FT MOD_RES 567
FT /note="Phosphothreonine; by ROCK2 and PKC/PRKCI"
FT /evidence="ECO:0000305|PubMed:18270268"
FT VARIANT 180
FT /note="R -> C (in dbSNP:rs3103004)"
FT /id="VAR_030572"
FT VARIANT 494
FT /note="A -> P (in dbSNP:rs2230143)"
FT /id="VAR_030573"
FT VARIANT 532
FT /note="L -> V"
FT /evidence="ECO:0000269|PubMed:2591371,
FT ECO:0000269|PubMed:2674140"
FT /id="VAR_015112"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 15..20
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 26..37
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 45..51
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:4RM8"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 74..84
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 96..111
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 119..134
FT /evidence="ECO:0007829|PDB:4RMA"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:4RMA"
FT TURN 144..149
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 155..159
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 165..178
FT /evidence="ECO:0007829|PDB:4RMA"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 184..196
FT /evidence="ECO:0007829|PDB:4RMA"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 204..210
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 224..229
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 245..251
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 254..261
FT /evidence="ECO:0007829|PDB:4RMA"
FT STRAND 267..270
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 274..295
FT /evidence="ECO:0007829|PDB:4RMA"
FT HELIX 520..523
FT /evidence="ECO:0007829|PDB:4RM8"
FT HELIX 525..539
FT /evidence="ECO:0007829|PDB:4RM8"
FT HELIX 544..546
FT /evidence="ECO:0007829|PDB:4RM8"
FT HELIX 549..559
FT /evidence="ECO:0007829|PDB:4RM8"
FT HELIX 564..571
FT /evidence="ECO:0007829|PDB:4RM8"
FT HELIX 576..585
FT /evidence="ECO:0007829|PDB:4RM8"
SQ SEQUENCE 586 AA; 69413 MW; F1B592CF49A7CC46 CRC64;
MPKPINVRVT TMDAELEFAI QPNTTGKQLF DQVVKTIGLR EVWYFGLHYV DNKGFPTWLK
LDKKVSAQEV RKENPLQFKF RAKFYPEDVA EELIQDITQK LFFLQVKEGI LSDEIYCPPE
TAVLLGSYAV QAKFGDYNKE VHKSGYLSSE RLIPQRVMDQ HKLTRDQWED RIQVWHAEHR
GMLKDNAMLE YLKIAQDLEM YGINYFEIKN KKGTDLWLGV DALGLNIYEK DDKLTPKIGF
PWSEIRNISF NDKKFVIKPI DKKAPDFVFY APRLRINKRI LQLCMGNHEL YMRRRKPDTI
EVQQMKAQAR EEKHQKQLER QQLETEKKRR ETVEREKEQM MREKEELMLR LQDYEEKTKK
AERELSEQIQ RALQLEEERK RAQEEAERLE ADRMAALRAK EELERQAVDQ IKSQEQLAAE
LAEYTAKIAL LEEARRRKED EVEEWQHRAK EAQDDLVKTK EELHLVMTAP PPPPPPVYEP
VSYHVQESLQ DEGAEPTGYS AELSSEGIRD DRNEEKRITE AEKNERVQRQ LLTLSSELSQ
ARDENKRTHN DIIHNENMRQ GRDKYKTLRQ IRQGNTKQRI DEFEAL
