EZRI_BOVIN
ID EZRI_BOVIN Reviewed; 581 AA.
AC P31976; Q3ZCB9;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Ezrin;
DE AltName: Full=Cytovillin;
DE AltName: Full=Villin-2;
DE AltName: Full=p81;
GN Name=EZR; Synonyms=VIL2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Bergson C.M., Zhao H., Saijoh K., Duman R.S., Nestler E.J.;
RT "Ezrin and osteonectin, two proteins associated with cell shape and growth,
RT are enriched in the locus coeruleus.";
RL Mol. Cell. Neurosci. 4:64-73(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 2-16 AND 127-141.
RC TISSUE=Kidney;
RX PubMed=8660651; DOI=10.1006/abbi.1996.0248;
RA Galat A., Gerbod M.C., Bouet F., Riviere S.;
RT "Proteins and their amino acid compositions: uniqueness, variability, and
RT applications.";
RL Arch. Biochem. Biophys. 330:229-237(1996).
RN [4]
RP IDENTIFICATION IN A COMPLEX WITH PRX; AHNAK AND PPL, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=14625392; DOI=10.1242/jcs.00815;
RA Straub B.K., Boda J., Kuhn C., Schnoelzer M., Korf U., Kempf T., Spring H.,
RA Hatzfeld M., Franke W.W.;
RT "A novel cell-cell junction system: the cortex adhaerens mosaic of lens
RT fiber cells.";
RL J. Cell Sci. 116:4985-4995(2003).
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 (By
CC similarity). {ECO:0000250}.
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: Interacts with PALS1 and SLC9A3R2. Found in a complex with
CC EZR, PODXL and SLC9A3R2. Interacts with MCC, PLEKHG6, PODXL,
CC SCYL3/PACE1, SLC9A3R1 and TMEM8B. Interacts (when phosphorylated) with
CC FES/FPS. Interacts with dimeric S100P, the interaction may be
CC activating through unmasking of F-actin binding sites. 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 (PubMed:14625392). Interacts with PDPN
CC (via cytoplasmic domain); activates RHOA and promotes epithelial-
CC mesenchymal transition. Interacts with SPN/CD43 cytoplasmic tail, CD44
CC and ICAM2 (By similarity). {ECO:0000250|UniProtKB:P15311,
CC ECO:0000250|UniProtKB:P26040, ECO:0000250|UniProtKB:P31977,
CC ECO:0000250|UniProtKB:Q8HZQ5, ECO:0000269|PubMed:14625392}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:P15311}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P15311}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P15311}. Cell projection
CC {ECO:0000250|UniProtKB:P15311}. Cell projection, microvillus membrane
CC {ECO:0000250|UniProtKB:P15311}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P15311}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P15311}. Cell projection, ruffle membrane
CC {ECO:0000250|UniProtKB:P15311}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P15311}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P15311}. Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:P15311}. Cytoplasm, cytoskeleton
CC {ECO:0000305|PubMed:14625392}. 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 Microvillar peripheral membrane protein (cytoplasmic side). Localizes
CC to cell extensions and peripheral processes of astrocytes (By
CC similarity). {ECO:0000250|UniProtKB:P15311,
CC ECO:0000250|UniProtKB:P31977}.
CC -!- TISSUE SPECIFICITY: Detected in eye lens fiber cells (at protein
CC level). {ECO:0000269|PubMed:14625392}.
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:0000250|UniProtKB:P15311}.
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 581) 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:0000250|UniProtKB:P15311}.
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:0000250|UniProtKB:P15311}.
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:0000250|UniProtKB:P15311}.
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:0000250|UniProtKB:P15311}.
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DR EMBL; M98498; AAA30510.1; -; mRNA.
DR EMBL; BC102573; AAI02574.1; -; mRNA.
DR PIR; I45889; I45889.
DR RefSeq; NP_776642.1; NM_174217.2.
DR RefSeq; XP_010799028.1; XM_010800726.2.
DR AlphaFoldDB; P31976; -.
DR BMRB; P31976; -.
DR SMR; P31976; -.
DR CORUM; P31976; -.
DR STRING; 9913.ENSBTAP00000013663; -.
DR PaxDb; P31976; -.
DR PeptideAtlas; P31976; -.
DR PRIDE; P31976; -.
DR Ensembl; ENSBTAT00000013663; ENSBTAP00000013663; ENSBTAG00000010347.
DR GeneID; 281574; -.
DR KEGG; bta:281574; -.
DR CTD; 7430; -.
DR VEuPathDB; HostDB:ENSBTAG00000010347; -.
DR VGNC; VGNC:28676; EZR.
DR eggNOG; KOG3529; Eukaryota.
DR GeneTree; ENSGT00960000186596; -.
DR HOGENOM; CLU_003623_6_2_1; -.
DR InParanoid; P31976; -.
DR OrthoDB; 627741at2759; -.
DR TreeFam; TF313935; -.
DR Proteomes; UP000009136; Chromosome 9.
DR Bgee; ENSBTAG00000010347; Expressed in oocyte and 105 other tissues.
DR ExpressionAtlas; P31976; baseline and differential.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005884; C:actin filament; ISS:UniProtKB.
DR GO; GO:0005912; C:adherens junction; IBA:GO_Central.
DR GO; GO:0045177; C:apical part of cell; ISS:AgBase.
DR GO; GO:0016324; C:apical plasma membrane; ISS:AgBase.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0036064; C:ciliary basal body; ISS:AgBase.
DR GO; GO:0019898; C:extrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0030175; C:filopodium; IBA:GO_Central.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001931; C:uropod; ISS:AgBase.
DR GO; GO:0003779; F:actin binding; IBA:GO_Central.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
DR GO; GO:0050839; F:cell adhesion molecule binding; ISS:UniProtKB.
DR GO; GO:0051017; P:actin filament bundle assembly; ISS:UniProtKB.
DR GO; GO:0035088; P:establishment or maintenance of apical/basal cell polarity; ISS:AgBase.
DR GO; GO:2000643; P:positive regulation of early endosome to late endosome transport; IBA:GO_Central.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; IBA:GO_Central.
DR GO; GO:0008360; P:regulation of cell shape; IBA:GO_Central.
DR GO; GO:1902115; P:regulation of organelle assembly; IBA:GO_Central.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd13194; FERM_C_ERM; 1.
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 Acetylation; Cell membrane; Cell projection; Cell shape; Coiled coil;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Membrane;
KW Phosphoprotein; Reference proteome; S-nitrosylation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8660651"
FT CHAIN 2..581
FT /note="Ezrin"
FT /id="PRO_0000219407"
FT DOMAIN 2..295
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT REGION 244..581
FT /note="Interaction with SCYL3"
FT /evidence="ECO:0000250"
FT REGION 306..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..560
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:0000250|UniProtKB:P15311"
FT COMPBIAS 535..560
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 60
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P15311"
FT MOD_RES 146
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000250|UniProtKB:P15311"
FT MOD_RES 354
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000250|UniProtKB:P15311"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15311"
FT MOD_RES 476
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P15311"
FT MOD_RES 562
FT /note="Phosphothreonine; by ROCK2 and PKC/PRKCI"
FT /evidence="ECO:0000250|UniProtKB:P15311"
SQ SEQUENCE 581 AA; 68760 MW; B00D3FBCD294EAD7 CRC64;
MPKPINVRVT TMDAELEFAI QPNTTGKQLF DQVVKTIGLR EVWYFGLQYV DNKGFPTWLK
LDKKVSAQEV RKESPLQFKF RAKFYPEDVA EELIQDITQK LFFLQVKEGI LSDEIYCPPE
TAVLLGSYAV QAKFGDYNKE LHKAGYLGSE RLIPQRVMDQ HKLTRDQWED RIQVWHAEHR
GMLKDSAMLE YLKIAQDLEM YGINYFEIKN KKGTDLWLGV DALGLNIYEK DDKLTPKIGF
PWSEIRNISF NDKKFVIKPI DKKAPDFVFY APRLRINKRI LQLCMGNHEL YMRRRKPDTI
EVQQMKAQAR EEKHQKQLER QQLETEKKRR ETVEREKEQM MREKEELMLR LQDYEEKTRK
AEKELSDQIQ RALKLEEERK RAQEEAGRLE ADRLAALRAK EELERQAADQ IKSQEQLATE
LAEYTAKIAL LEEARRRKEN EVEEWQLRAK EAQDDLVKTR EELHLVMTAP PPPPVYEPVN
YHVHEGPQEE GTELSAELSS EGILDDRNEE KRITEAEKNE RVQRQLMTLT SELSQARDEN
KRTHNDIIHN ENMRQGRDKY KTLRQIRQGN TKQRIDEFEA M
