UniProtKB - P15311 (EZRI_HUMAN)
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Protein
Ezrin
Gene
EZR
Organism
Homo sapiens (Human)
Status
Functioni
Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis.3 Publications
Enzyme regulationi
A head-to-tail association, of the N-terminal and C-terminal halves results in a closed conformation (inactive form) which is incapable of actin or membrane-binding.By similarity
GO - Molecular functioni
- actin binding Source: UniProtKB
- actin filament binding Source: UniProtKB
- ATPase binding Source: UniProtKB
- cadherin binding Source: BHF-UCL
- cell adhesion molecule binding Source: BHF-UCL
- disordered domain specific binding Source: Ensembl
- microtubule binding Source: UniProtKB
- protein C-terminus binding Source: Ensembl
- protein domain specific binding Source: UniProtKB
- protein kinase A catalytic subunit binding Source: UniProtKB
- protein kinase A regulatory subunit binding Source: UniProtKB
- RNA binding Source: UniProtKB
- S100 protein binding Source: UniProtKB
GO - Biological processi
- actin cytoskeleton reorganization Source: UniProtKB
- actin filament bundle assembly Source: UniProtKB
- astral microtubule organization Source: UniProtKB
- axon guidance Source: Reactome
- cellular protein complex localization Source: UniProtKB
- cellular response to cAMP Source: UniProtKB
- cortical microtubule organization Source: UniProtKB
- cytoskeletal anchoring at plasma membrane Source: UniProtKB
- establishment of centrosome localization Source: UniProtKB
- establishment of endothelial barrier Source: UniProtKB
- establishment of protein localization to plasma membrane Source: UniProtKB
- establishment or maintenance of apical/basal cell polarity Source: Ensembl
- filopodium assembly Source: UniProtKB
- intestinal D-glucose absorption Source: Ensembl
- leukocyte cell-cell adhesion Source: BHF-UCL
- membrane to membrane docking Source: BHF-UCL
- microvillus assembly Source: UniProtKB
- negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
- negative regulation of interleukin-2 secretion Source: UniProtKB
- negative regulation of p38MAPK cascade Source: UniProtKB
- negative regulation of T cell receptor signaling pathway Source: UniProtKB
- negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
- phosphatidylinositol-mediated signaling Source: UniProtKB
- positive regulation of cellular protein catabolic process Source: UniProtKB
- positive regulation of early endosome to late endosome transport Source: UniProtKB
- positive regulation of establishment of protein localization to plasma membrane Source: Ensembl
- positive regulation of gene expression Source: UniProtKB
- positive regulation of multicellular organism growth Source: Ensembl
- positive regulation of protein localization to early endosome Source: UniProtKB
- positive regulation of protein secretion Source: UniProtKB
- protein kinase A signaling Source: UniProtKB
- protein localization to cell cortex Source: UniProtKB
- receptor internalization Source: Ensembl
- regulation of cell shape Source: UniProtKB
- regulation of microvillus length Source: Ensembl
- regulation of organelle assembly Source: UniProtKB
- sphingosine-1-phosphate signaling pathway Source: UniProtKB
- terminal web assembly Source: Ensembl
Keywordsi
| Biological process | Cell shape |
Enzyme and pathway databases
| Reactomei | R-HSA-373752. Netrin-1 signaling. R-HSA-437239. Recycling pathway of L1. |
| SIGNORi | P15311. |
Names & Taxonomyi
| Protein namesi | Recommended name: EzrinAlternative name(s): Cytovillin Villin-2 p81 |
| Gene namesi | Name:EZR Synonyms:VIL2 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:12691. EZR. |
Subcellular locationi
- Apical cell membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
- Cell projection 1 Publication
- Cell projection › microvillus membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
- Cell projection › ruffle membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
- Cytoplasm › cell cortex 1 Publication
- Cytoplasm › cytoskeleton 1 Publication
Note: Localization to the apical membrane of parietal cells depends on the interaction with MPP5. Localizes to cell extensions and peripheral processes of astrocytes (By similarity). Microvillar peripheral membrane protein (cytoplasmic side).By similarity
GO - Cellular componenti
- actin cytoskeleton Source: UniProtKB
- actin filament Source: HGNC
- apical part of cell Source: BHF-UCL
- apical plasma membrane Source: UniProtKB
- astrocyte projection Source: Ensembl
- basolateral plasma membrane Source: UniProtKB
- brush border Source: UniProtKB
- cell body Source: Ensembl
- cell periphery Source: UniProtKB
- cell projection Source: UniProtKB
- cell tip Source: Ensembl
- ciliary basal body Source: Ensembl
- cortical cytoskeleton Source: HGNC
- cytoplasm Source: UniProtKB
- cytoplasmic side of apical plasma membrane Source: UniProtKB
- cytosol Source: UniProtKB
- endosome Source: UniProtKB
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
- extrinsic component of membrane Source: UniProtKB
- fibrillar center Source: HPA
- filopodium Source: UniProtKB
- focal adhesion Source: UniProtKB
- immunological synapse Source: UniProtKB
- membrane Source: UniProtKB
- microspike Source: Ensembl
- microvillus Source: BHF-UCL
- microvillus membrane Source: UniProtKB-SubCell
- myelin sheath Source: Ensembl
- perinuclear region of cytoplasm Source: UniProtKB
- plasma membrane Source: UniProtKB
- plasma membrane raft Source: UniProtKB
- ruffle Source: UniProtKB
- ruffle membrane Source: UniProtKB-SubCell
- Schwann cell microvillus Source: Ensembl
- T-tubule Source: Ensembl
- uropod Source: Ensembl
- vesicle Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, MembranePathology & Biotechi
Organism-specific databases
| DisGeNETi | 7430. |
| MalaCardsi | EZR. |
| OpenTargetsi | ENSG00000092820. |
| PharmGKBi | PA162385512. |
Chemistry databases
| ChEMBLi | CHEMBL1932896. |
Polymorphism and mutation databases
| BioMutai | EZR. |
| DMDMi | 125987826. |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Initiator methioninei | RemovedBy similarity | |||
| ChainiPRO_0000219408 | 2 – 586 | EzrinAdd BLAST | 585 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 60 | N6-acetyllysineCombined sources | 1 | |
| Modified residuei | 146 | Phosphotyrosine; by PDGFR2 Publications | 1 | |
| Modified residuei | 354 | Phosphotyrosine; by PDGFR1 Publication | 1 | |
| Modified residuei | 366 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 478 | Phosphotyrosine1 Publication | 1 | |
| Modified residuei | 535 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 567 | Phosphothreonine; by ROCK2 and PKC/PRKCI1 Publication | 1 |
Post-translational modificationi
Phosphorylated by tyrosine-protein kinases. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding (By similarity).By similarity
S-nitrosylation is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) possibly implicating the iNOS-S100A8/9 transnitrosylase complex.1 Publication
Keywords - PTMi
Acetylation, Phosphoprotein, S-nitrosylationProteomic databases
| EPDi | P15311. |
| MaxQBi | P15311. |
| PaxDbi | P15311. |
| PeptideAtlasi | P15311. |
| PRIDEi | P15311. |
| TopDownProteomicsi | P15311. |
2D gel databases
| DOSAC-COBS-2DPAGEi | P15311. |
| REPRODUCTION-2DPAGEi | IPI00843975. |
| SWISS-2DPAGEi | P15311. |
PTM databases
| iPTMneti | P15311. |
| PhosphoSitePlusi | P15311. |
| SwissPalmi | P15311. |
Expressioni
Tissue specificityi
Expressed in cerebral cortex, basal ganglia, hippocampus, hypophysis, and optic nerve. Weakly expressed in brain stem and diencephalon. Stronger expression was detected in gray matter of frontal lobe compared to white matter (at protein level). Component of the microvilli of intestinal epithelial cells. Preferentially expressed in astrocytes of hippocampus, frontal cortex, thalamus, parahippocampal cortex, amygdala, insula, and corpus callosum. Not detected in neurons in most tissues studied.1 Publication
Developmental stagei
Very strong staining is detected in the Purkinje cell layer and in part of the molecular layer of the infant brain compared to adult brain.1 Publication
Gene expression databases
| Bgeei | ENSG00000092820. |
| CleanExi | HS_EZR. |
| ExpressionAtlasi | P15311. baseline and differential. |
| Genevisiblei | P15311. HS. |
Organism-specific databases
| HPAi | CAB004035. CAB047324. HPA021616. |
Interactioni
Subunit structurei
Interacts with MPP5 and SLC9A3R2. Found in a complex with EZR, PODXL and SLC9A3R2 (By similarity). Interacts with MCC, PLEKHG6, PODXL, SCYL3/PACE1, SLC9A3R1 and TMEM8B (PubMed:9314537, PubMed:12651155, PubMed:15498789, PubMed:17616675, PubMed:17881735, PubMed:19555689). Interacts (when phosphorylated) with FES/FPS (PubMed:18046454). Interacts with dimeric S100P, the interaction may be activating through unmasking of F-actin binding sites (PubMed:12808036, PubMed:19111582). Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (By similarity). Detected in a complex composed of at least EZR, AHNAK, PPL and PRX (By similarity).By similarity9 Publications
Binary interactionsi
GO - Molecular functioni
- actin binding Source: UniProtKB
- actin filament binding Source: UniProtKB
- ATPase binding Source: UniProtKB
- cadherin binding Source: BHF-UCL
- cell adhesion molecule binding Source: BHF-UCL
- disordered domain specific binding Source: Ensembl
- microtubule binding Source: UniProtKB
- protein C-terminus binding Source: Ensembl
- protein domain specific binding Source: UniProtKB
- protein kinase A catalytic subunit binding Source: UniProtKB
- protein kinase A regulatory subunit binding Source: UniProtKB
- S100 protein binding Source: UniProtKB
Protein-protein interaction databases
| BioGridi | 113271. 144 interactors. |
| DIPi | DIP-38868N. |
| IntActi | P15311. 38 interactors. |
| MINTi | MINT-195721. |
| STRINGi | 9606.ENSP00000338934. |
Chemistry databases
| BindingDBi | P15311. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Beta strandi | 5 – 10 | Combined sources | 6 | |
| Beta strandi | 15 – 20 | Combined sources | 6 | |
| Helixi | 26 – 37 | Combined sources | 12 | |
| Helixi | 42 – 44 | Combined sources | 3 | |
| Beta strandi | 45 – 51 | Combined sources | 7 | |
| Beta strandi | 56 – 58 | Combined sources | 3 | |
| Beta strandi | 61 – 64 | Combined sources | 4 | |
| Helixi | 65 – 67 | Combined sources | 3 | |
| Beta strandi | 74 – 84 | Combined sources | 11 | |
| Helixi | 89 – 92 | Combined sources | 4 | |
| Helixi | 96 – 111 | Combined sources | 16 | |
| Helixi | 119 – 134 | Combined sources | 16 | |
| Turni | 139 – 141 | Combined sources | 3 | |
| Turni | 144 – 149 | Combined sources | 6 | |
| Helixi | 155 – 159 | Combined sources | 5 | |
| Helixi | 165 – 178 | Combined sources | 14 | |
| Turni | 179 – 181 | Combined sources | 3 | |
| Helixi | 184 – 196 | Combined sources | 13 | |
| Turni | 199 – 202 | Combined sources | 4 | |
| Beta strandi | 204 – 210 | Combined sources | 7 | |
| Beta strandi | 215 – 221 | Combined sources | 7 | |
| Beta strandi | 224 – 229 | Combined sources | 6 | |
| Beta strandi | 233 – 235 | Combined sources | 3 | |
| Beta strandi | 237 – 241 | Combined sources | 5 | |
| Helixi | 242 – 244 | Combined sources | 3 | |
| Beta strandi | 245 – 251 | Combined sources | 7 | |
| Beta strandi | 254 – 261 | Combined sources | 8 | |
| Beta strandi | 267 – 270 | Combined sources | 4 | |
| Helixi | 274 – 295 | Combined sources | 22 | |
| Helixi | 520 – 523 | Combined sources | 4 | |
| Helixi | 525 – 539 | Combined sources | 15 | |
| Helixi | 544 – 546 | Combined sources | 3 | |
| Helixi | 549 – 559 | Combined sources | 11 | |
| Helixi | 564 – 571 | Combined sources | 8 | |
| Helixi | 576 – 585 | Combined sources | 10 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1NI2 | X-ray | 2.30 | A/B | 2-297 | [»] | |
| 4RM8 | X-ray | 1.90 | A/B | 1-586 | [»] | |
| 4RM9 | X-ray | 2.00 | A | 1-586 | [»] | |
| 4RMA | X-ray | 1.75 | A/B | 1-296 | [»] | |
| DisProti | DP00775. | |||||
| ProteinModelPortali | P15311. | |||||
| SMRi | P15311. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Miscellaneous databases
| EvolutionaryTracei | P15311. |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 2 – 295 | FERMPROSITE-ProRule annotationAdd BLAST | 294 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 244 – 586 | Interaction with SCYL31 PublicationAdd BLAST | 343 |
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Motifi | 115 – 120 | [IL]-x-C-x-x-[DE] motif1 Publication | 6 |
Domaini
The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.1 Publication
Phylogenomic databases
| eggNOGi | KOG3529. Eukaryota. ENOG410XQFP. LUCA. |
| GeneTreei | ENSGT00860000133686. |
| HOGENOMi | HOG000007113. |
| HOVERGENi | HBG002185. |
| InParanoidi | P15311. |
| KOi | K08007. |
| PhylomeDBi | P15311. |
| TreeFami | TF313935. |
Family and domain databases
| CDDi | cd14473. FERM_B-lobe. 1 hit. |
| Gene3Di | 1.20.80.10. 2 hits. 2.30.29.30. 1 hit. |
| InterProi | View protein in InterPro IPR019749. Band_41_domain. IPR011174. ERM. IPR011259. ERM_C_dom. IPR000798. Ez/rad/moesin-like. IPR014352. FERM/acyl-CoA-bd_prot_3-hlx. IPR019748. FERM_central. IPR019747. FERM_CS. IPR000299. FERM_domain. IPR018979. FERM_N. IPR018980. FERM_PH-like_C. IPR008954. Moesin_tail. IPR011993. PH_dom-like. IPR029071. Ubiquitin-rel_dom. |
| Pfami | View protein in Pfam PF00769. ERM. 1 hit. PF09380. FERM_C. 1 hit. PF00373. FERM_M. 1 hit. PF09379. FERM_N. 1 hit. |
| PIRSFi | PIRSF002305. ERM. 1 hit. |
| PRINTSi | PR00935. BAND41. PR00661. ERMFAMILY. |
| SMARTi | View protein in SMART SM00295. B41. 1 hit. SM01196. FERM_C. 1 hit. |
| SUPFAMi | SSF47031. SSF47031. 1 hit. SSF48678. SSF48678. 1 hit. SSF50729. SSF50729. 1 hit. SSF54236. SSF54236. 1 hit. |
| PROSITEi | View protein in PROSITE PS00660. FERM_1. 1 hit. PS00661. FERM_2. 1 hit. PS50057. FERM_3. 1 hit. |
Sequencei
Sequence statusi: Complete.
Sequence processingi: The displayed sequence is further processed into a mature form.
P15311-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPKPINVRVT TMDAELEFAI QPNTTGKQLF DQVVKTIGLR EVWYFGLHYV
60 70 80 90 100
DNKGFPTWLK LDKKVSAQEV RKENPLQFKF RAKFYPEDVA EELIQDITQK
110 120 130 140 150
LFFLQVKEGI LSDEIYCPPE TAVLLGSYAV QAKFGDYNKE VHKSGYLSSE
160 170 180 190 200
RLIPQRVMDQ HKLTRDQWED RIQVWHAEHR GMLKDNAMLE YLKIAQDLEM
210 220 230 240 250
YGINYFEIKN KKGTDLWLGV DALGLNIYEK DDKLTPKIGF PWSEIRNISF
260 270 280 290 300
NDKKFVIKPI DKKAPDFVFY APRLRINKRI LQLCMGNHEL YMRRRKPDTI
310 320 330 340 350
EVQQMKAQAR EEKHQKQLER QQLETEKKRR ETVEREKEQM MREKEELMLR
360 370 380 390 400
LQDYEEKTKK AERELSEQIQ RALQLEEERK RAQEEAERLE ADRMAALRAK
410 420 430 440 450
EELERQAVDQ IKSQEQLAAE LAEYTAKIAL LEEARRRKED EVEEWQHRAK
460 470 480 490 500
EAQDDLVKTK EELHLVMTAP PPPPPPVYEP VSYHVQESLQ DEGAEPTGYS
510 520 530 540 550
AELSSEGIRD DRNEEKRITE AEKNERVQRQ LLTLSSELSQ ARDENKRTHN
560 570 580
DIIHNENMRQ GRDKYKTLRQ IRQGNTKQRI DEFEAL
Sequence cautioni
The sequence AAA61278 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAB82418 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_030572 | 180 | R → C. Corresponds to variant dbSNP:rs3103004Ensembl. | 1 | |
| Natural variantiVAR_030573 | 494 | A → P. Corresponds to variant dbSNP:rs2230143Ensembl. | 1 | |
| Natural variantiVAR_015112 | 532 | L → V2 Publications | 1 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X51521 mRNA. Translation: CAA35893.1. J05021 mRNA. Translation: AAA61278.1. Different initiation. AL162086 mRNA. Translation: CAB82418.1. Different initiation. AL589931 Genomic DNA. No translation available. CH471051 Genomic DNA. Translation: EAW47647.1. BC013903 mRNA. Translation: AAH13903.1. |
| CCDSi | CCDS5258.1. |
| PIRi | A34400. |
| RefSeqi | NP_001104547.1. NM_001111077.1. NP_003370.2. NM_003379.4. |
| UniGenei | Hs.487027. |
Genome annotation databases
| Ensembli | ENST00000337147; ENSP00000338934; ENSG00000092820. ENST00000367075; ENSP00000356042; ENSG00000092820. |
| GeneIDi | 7430. |
| KEGGi | hsa:7430. |
| UCSCi | uc003qrt.5. human. |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:| 100% | UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry. |
| 90% | UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence). |
| 50% | UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster. |
Entry informationi
| Entry namei | EZRI_HUMAN | |
| Accessioni | P15311Primary (citable) accession number: P15311 Secondary accession number(s): E1P5A8 Q9NSJ4 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1990 |
| Last sequence update: | February 6, 2007 | |
| Last modified: | July 5, 2017 | |
| This is version 198 of the entry and version 4 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references
