EZRI_RABIT
ID EZRI_RABIT Reviewed; 586 AA.
AC Q8HZQ5;
DT 27-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 25-MAY-2022, entry version 118.
DE RecName: Full=Ezrin;
DE AltName: Full=Cytovillin;
DE AltName: Full=Villin-2;
DE AltName: Full=p81;
GN Name=EZR; Synonyms=VIL2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white;
RA Goldenring J.R.;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INTERACTION WITH PALS1, AND SUBCELLULAR LOCATION.
RX PubMed=15677456; DOI=10.1074/jbc.m411941200;
RA Cao X., Ding X., Guo Z., Zhou R., Wang F., Long F., Wu F., Bi F., Wang Q.,
RA Fan D., Forte J.G., Teng M., Yao X.;
RT "PALS1 specifies the localization of Ezrin to the apical membrane of
RT gastric parietal cells.";
RL J. Biol. Chem. 280:13584-13592(2005).
CC -!- FUNCTION: Probably involved in connections of major cytoskeletal
CC structures to the plasma membrane (By similarity). In epithelial cells,
CC required for the formation of microvilli and membrane ruffles on the
CC apical pole. Along with PLEKHG6, required for normal macropinocytosis
CC (By 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 (PubMed:15677456). Found in a complex
CC with EZR, PODXL and SLC9A3R2. Interacts with MCC, PLEKHG6, PODXL,
CC SCYL3/PACE1, SLC9A3R1, SLC9A3R2 and TMEM8B. Interacts (when
CC phosphorylated) with FES/FPS. Interacts with dimeric S100P, the
CC interaction may be activating through unmasking of F-actin binding
CC sites. Identified in complexes that contain VIM, EZR, AHNAK, BFSP1,
CC BFSP2, ANK2, PLEC, PRX and spectrin. Detected in a complex composed of
CC at least EZR, AHNAK, PPL and PRX. Interacts with PDPN (via cytoplasmic
CC domain); activates RHOA and promotes epithelial-mesenchymal transition.
CC Interacts with SPN/CD43 cytoplasmic tail, CD44 and ICAM2 (By
CC similarity). {ECO:0000250|UniProtKB:P15311,
CC ECO:0000250|UniProtKB:P26040, ECO:0000250|UniProtKB:P31976,
CC ECO:0000250|UniProtKB:P31977, ECO:0000269|PubMed:15677456}.
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:0000250|UniProtKB:P15311}. Cell projection, microvillus
CC {ECO:0000250|UniProtKB:P26040}. Note=Localizes to cell extensions and
CC peripheral processes of astrocytes (By similarity). Microvillar
CC peripheral membrane protein (cytoplasmic side). Localization to the
CC apical membrane of parietal cells depends on the interaction with
CC PALS1. {ECO:0000250|UniProtKB:P15311, ECO:0000250|UniProtKB:P31977,
CC ECO:0000269|PubMed:15677456}.
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 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: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; AF537266; AAN06818.1; -; mRNA.
DR RefSeq; NP_001075591.1; NM_001082122.1.
DR AlphaFoldDB; Q8HZQ5; -.
DR SMR; Q8HZQ5; -.
DR STRING; 9986.ENSOCUP00000003322; -.
DR iPTMnet; Q8HZQ5; -.
DR PRIDE; Q8HZQ5; -.
DR GeneID; 100008846; -.
DR KEGG; ocu:100008846; -.
DR CTD; 7430; -.
DR eggNOG; KOG3529; Eukaryota.
DR InParanoid; Q8HZQ5; -.
DR OrthoDB; 627741at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005884; C:actin filament; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
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:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
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; Membrane; Phosphoprotein; Reference proteome;
KW S-nitrosylation.
FT CHAIN 1..586
FT /note="Ezrin"
FT /id="PRO_0000219410"
FT DOMAIN 2..295
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT REGION 244..586
FT /note="Interaction with SCYL3"
FT /evidence="ECO:0000250"
FT REGION 305..340
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 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 478
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P15311"
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:0000250|UniProtKB:P15311"
SQ SEQUENCE 586 AA; 69220 MW; FA2467B72E4B365E CRC64;
MPKPINVRVT TMDAELEFAV QPNTTGKQLF DQVVKTIGLR EVWYFGLQYV DNKGFPTWLK
LDKKVSAQEV RKENPVQFKF RAKFYPEDVS EELIQDITQK LFFLQVKEGI LSDEIYCPPE
TAVLLGSYAV QAKFGDYSKE AHKAGYLSSE RLIPQRVMDQ HKLSRDQWED RIQVWHAEHR
GMLKDSAMLE YLKIAQDLEM YGINYFEIKN KKGTDLWLGV DALGLNIYEK NDKLTPKIGF
PWSEIRNISF NDKKFVIKPI DKKAPDFVFY APRLRINKRI LQLCMGNHEL YMRRRKPDTI
EVQQMKAQAR EEKHQKQLER QQLESEKKRR EAVEQEKEQM LREKEELMMR LQDYEQKTKK
AEKELSDQIQ RALQLEDERK RAQEESERLE ADRVAALRAK EELERQAADQ IKSQEQLAAE
LAEYTAKIAL LEEARRRKES EVEEWQHRAR EAQDDLVKTK EELHLVMTAP PPPPPPMYEP
VSYHVQEHLH EEGAESLGYS AELSSEGILD DRHEEKRITE AEKNERVQRQ LLTLSNELSQ
ARDENKRTHN DIIHNENLRQ GRDKYKTLRQ IRQGNTKQRI DEFEAM
