Reviewed, UniProtKB/Swiss-Prot P15311 (EZRI_HUMAN)

Names and origin

Protein names

Recommended name:
    Ezrin
Alternative name(s):
    p81
    Cytovillin
    Villin-2

Gene names

Name:	EZR
Synonyms:	VIL2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	586 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. Ref.14
Subunit structure	Interacts with MPP5 By similarity. Interacts with SLC9A3R1 and SCYL3/PACE1. Interacts with PLEKHG6. Interacts with NGX6.
Subcellular location	Apical cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection. Cell projection › microvillus membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection › ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm › cell cortex. Cytoplasm › cytoskeleton. 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).
Tissue specificity	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. Ref.13
Developmental stage	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. Ref.13
Post-translational modification	Phosphorylated by tyrosine-protein kinases. Ref.8 Ref.9
Sequence similarities	Contains 1 FERM domain.

Ontologies

Keywords
Biological process	Cell shape
Cellular component	Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Polymorphism
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	actin filament bundle formation Inferred from direct assay. Source: UniProtKB cytoskeletal anchoring at plasma membrane Non-traceable author statement. Source: UniProtKB leukocyte adhesion Inferred from expression pattern. Source: UniProtKB membrane to membrane docking Inferred from expression pattern. Source: UniProtKB regulation of cell shape Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	actin filament Inferred from direct assay. Source: HGNC apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cortical cytoskeleton Traceable author statement. Source: HGNC cytosol Inferred from direct assay. Source: UniProtKB extrinsic to membrane Inferred from direct assay. Source: UniProtKB filopodium Inferred from direct assay. Source: UniProtKB microvillus membrane Inferred from electronic annotation. Source: UniProtKB-SubCell ruffle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	actin filament binding Inferred from direct assay. Source: UniProtKB cell adhesion molecule binding Ref.12 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GABARAPL2	P60520	1	EBI-1056902,EBI-720116
HLA-B	P30480	1	EBI-1056902,EBI-1054175
MCC	P23508	1	EBI-1056902,EBI-307531
PRKAB1	Q9Y478	1	EBI-1056902,EBI-719769
SCYL3	Q8IZE3	2	EBI-1056902,EBI-1380680

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 586

585

Ezrin

PRO_0000219408

Regions

Domain

2 – 295

294

FERM

Region

244 – 586

343

Interaction with SCYL3

Amino acid modifications

Modified residue

146

1

Phosphotyrosine; by PDGFR

Modified residue

354

1

Phosphotyrosine; by PDGFR

Natural variations

Natural variant

180

1

R → C: dbSNP rs3103004.

VAR_030572

Natural variant

494

1

A → P: dbSNP rs2230143.

VAR_030573

Natural variant

532

1

L → V Ref.1 Ref.2

VAR_015112

Secondary structure

1

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586

Helix Strand Turn

Details...

Beta strand

5 – 11

7

Beta strand

14 – 20

7

Helix

26 – 37

12

Helix

42 – 44

3

Beta strand

45 – 51

7

Beta strand

56 – 58

3

Beta strand

61 – 64

4

Helix

65 – 67

3

Beta strand

74 – 84

11

Helix

89 – 92

4

Helix

96 – 111

16

Helix

119 – 134

16

Turn

139 – 141

3

Beta strand

146 – 149

4

Helix

155 – 160

6

Helix

165 – 178

14

Helix

184 – 195

12

Turn

199 – 202

4

Beta strand

204 – 210

7

Beta strand

215 – 220

6

Beta strand

222 – 229

8

Beta strand

232 – 235

4

Beta strand

237 – 242

6

Beta strand

245 – 253

9

Beta strand

255 – 262

8

Beta strand

268 – 270

3

Helix

274 – 293

20

Sequences

	Sequence		Length	Mass (Da)
	P15311-1 [UniParc]. Last modified February 6, 2007. Version 4. Checksum: F1B592CF49A7CC46	FASTA	586	69,413
	10 20 30 40 50 60 MPKPINVRVT TMDAELEFAI QPNTTGKQLF DQVVKTIGLR EVWYFGLHYV DNKGFPTWLK 70 80 90 100 110 120 LDKKVSAQEV RKENPLQFKF RAKFYPEDVA EELIQDITQK LFFLQVKEGI LSDEIYCPPE 130 140 150 160 170 180 TAVLLGSYAV QAKFGDYNKE VHKSGYLSSE RLIPQRVMDQ HKLTRDQWED RIQVWHAEHR 190 200 210 220 230 240 GMLKDNAMLE YLKIAQDLEM YGINYFEIKN KKGTDLWLGV DALGLNIYEK DDKLTPKIGF 250 260 270 280 290 300 PWSEIRNISF NDKKFVIKPI DKKAPDFVFY APRLRINKRI LQLCMGNHEL YMRRRKPDTI 310 320 330 340 350 360 EVQQMKAQAR EEKHQKQLER QQLETEKKRR ETVEREKEQM MREKEELMLR LQDYEEKTKK 370 380 390 400 410 420 AERELSEQIQ RALQLEEERK RAQEEAERLE ADRMAALRAK EELERQAVDQ IKSQEQLAAE 430 440 450 460 470 480 LAEYTAKIAL LEEARRRKED EVEEWQHRAK EAQDDLVKTK EELHLVMTAP PPPPPPVYEP 490 500 510 520 530 540 VSYHVQESLQ DEGAEPTGYS AELSSEGIRD DRNEEKRITE AEKNERVQRQ LLTLSSELSQ 550 560 570 580 ARDENKRTHN DIIHNENMRQ GRDKYKTLRQ IRQGNTKQRI DEFEAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1." Gould K.L., Bretscher A., Esch F.S., Hunter T. EMBO J. 8:4133-4142(1989) [PubMed: 2591371] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT VAL-532.
[2]	"Cytovillin, a microvillar Mr 75,000 protein. cDNA sequence, prokaryotic expression, and chromosomal localization." Turunen O., Winqvist R., Pakkanen R., Grzeschik K.-H., Wahlstroem T., Vaheri A. J. Biol. Chem. 264:16727-16732(1989) [PubMed: 2674140] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-532. Tissue: Placenta.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Melanoma.
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[6]	"Identification of the 70kD heat shock cognate protein (Hsc70) and alpha-actinin-1 as novel phosphotyrosine-containing proteins in T lymphocytes." Egerton M., Moritz R.L., Druker B., Kelso A., Simpson R.J. Biochem. Biophys. Res. Commun. 224:666-674(1996) [PubMed: 8713105] [Abstract] Cited for: PROTEIN SEQUENCE OF 172-180 AND 343-350.
[7]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 264-273; 428-435 AND 530-542, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[8]	"Identification of the two major epidermal growth factor-induced tyrosine phosphorylation sites in the microvillar core protein ezrin." Krieg J., Hunter T. J. Biol. Chem. 267:19258-19265(1992) [PubMed: 1382070] [Abstract] Cited for: PHOSPHORYLATION BY PDGFR.
[9]	"Identification of ezrin as an 81-kDa tyrosine-phosphorylated protein in T cells." Egerton M., Burgess W.H., Chen D., Druker B.J., Bretscher A., Samelson L.E. J. Immunol. 149:1847-1852(1992) [PubMed: 1381389] [Abstract] Cited for: PHOSPHORYLATION.
[10]	"Identification of EBP50: a PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family." Reczek D., Berryman M., Bretscher A. J. Cell Biol. 139:169-179(1997) [PubMed: 9314537] [Abstract] Cited for: INTERACTION WITH SLC9A3R1.
[11]	"PACE-1, a novel protein that interacts with the C-terminal domain of ezrin." Sullivan A., Uff C.R., Isacke C.M., Thorne R.F. Exp. Cell Res. 284:224-238(2003) [PubMed: 12651155] [Abstract] Cited for: INTERACTION WITH SCYL3. Tissue: Kidney.
[12]	"Role of a novel EGF-like domain-containing gene NGX6 in cell adhesion modulation in nasopharyngeal carcinoma cells." Ma J., Zhou J., Fan S., Wang L.-L., Li X.-L., Yan Q., Zhou M., Liu H.-Y., Zhang Q., Zhou H., Gan K., Li Z., Peng C., Xiong W., Tan C., Shen S.-R., Yang J., Li J., Li G.-Y. Carcinogenesis 26:281-291(2005) [PubMed: 15498789] [Abstract] Cited for: INTERACTION WITH NGX6.
[13]	"Characterization of the NF2 protein merlin and the ERM protein ezrin in human, rat, and mouse central nervous system." Groenholm M., Teesalu T., Tyynelaa J., Piltti K., Boehling T., Wartiovaara K., Vaheri A., Carpen O. Mol. Cell. Neurosci. 28:683-693(2005) [PubMed: 15797715] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[14]	"Interaction of ezrin with the novel guanine nucleotide exchange factor PLEKHG6 promotes RhoG-dependent apical cytoskeleton rearrangements in epithelial cells." D'Angelo R., Aresta S., Blangy A., Del Maestro L., Louvard D., Arpin M. Mol. Biol. Cell 18:4780-4793(2007) [PubMed: 17881735] [Abstract] Cited for: FUNCTION, INTERACTION WITH PLEKHG6.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"Structure of the active N-terminal domain of Ezrin. Conformational and mobility changes identify keystone interactions." Smith W.J., Nassar N., Bretscher A., Cerione R.A., Karplus P.A. J. Biol. Chem. 278:4949-4956(2003) [PubMed: 12429733] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-297.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X51521 mRNA. Translation: CAA35893.1.
J05021 mRNA. Translation: AAA61278.1. Different initiation.
AL162086 mRNA. Translation: CAB82418.1. Different initiation.
AL589931 Genomic DNA. Translation: CAI95307.1.
BC013903 mRNA. Translation: AAH13903.1.

IPI

IPI00843975.

PIR

A34400.

RefSeq

NP_001104547.1.
NP_003370.2.

UniGene

Hs.487027

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NI2	X-ray	2.30	A/B	2-297	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P15311. 14 interactions.

PTM databases

PhosphoSite

P15311.

2-D gel databases

SWISS-2DPAGE

P15311.

DOSAC-COBS-2DPAGE

P15311.

REPRODUCTION-2DPAGE

IPI00843975.

Proteomic databases

PRIDE

P15311.

Genome annotation databases

Ensembl

ENSG00000092820. Homo sapiens. [Contig view]

GeneID

7430.

KEGG

hsa:7430.

UCSC

uc003qrt.2. human.

Organism-specific databases

GeneCards

GC06M159106.

HGNC

HGNC:12691. EZR.

HPA

CAB004035.

MIM

123900. gene.

PharmGKB

PA37310.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P15311.

Enzyme and pathway databases

Pathway_Interaction_DB

syndecan_2_pathway. Syndecan-2-mediated signaling events.

Gene expression databases

ArrayExpress

P15311.

Bgee

P15311.

CleanEx

HS_EZR.

GermOnline

ENSG00000092820. Homo sapiens.

Family and domain databases

InterPro

IPR019749. Band_41_domain.
IPR019750. Band_41_sg.
IPR011174. ERM.
IPR011259. ERM_C.
IPR000798. Ez/rad/moesin.
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.
IPR011993. PH_type.
[Graphical view]

Gene3D

G3DSA:1.20.80.10. ACBP. 1 hit.
G3DSA:2.30.29.30. PH_type. 1 hit.

Pfam

PF00769. ERM. 1 hit.
PF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
[Graphical view]

PIRSF

PIRSF002305. ERM. 1 hit.

PRINTS

PR00935. BAND41.
PR00661. ERMFAMILY.

SMART

SM00295. B41. 1 hit.
[Graphical view]

PROSITE

PS00660. FERM_1. 1 hit.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

29100.

SOURCE

Search...

Entry information

Entry name

EZRI_HUMAN

Accession

Primary (citable) accession number: P15311
Secondary accession number(s): P23714 , Q4VX75, Q96CU8, Q9NSJ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	February 6, 2007
Last modified:	July 7, 2009
This is version 112 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)