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O88339 (EPN1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Epsin-1
Alternative name(s):
EPS-15-interacting protein 1
Gene names
Name:Epn1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length575 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations. Regulates receptor-mediated endocytosis. Ref.1 Ref.7 Ref.10

Subunit structure

Monomer. Binds REPS2 and ITSN1 By similarity. Binds EPS15, clathrin, ZBTB16/ZNF145, AP2A1 and AP2A2. Binds ubiquitinated proteins. Interacts with RALBP1 in a complex also containing NUMB and TFAP2A during interphase and mitosis. Interacts with AP2B1. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein. Nucleus. Membraneclathrin-coated pit. Note: Associated with the cytoplasmic membrane at sites where clathrin-coated pits are forming. Colocalizes with clathrin and AP-2 in a punctate pattern on the plasma membrane. Colocalizes with clathrin at the Golgi complex. Detected in presynaptic nerve terminals and in synaptosomes. May shuttle to the nucleus when associated with ZBTB16/ZNF145. Ref.1 Ref.6 Ref.7 Ref.9

Tissue specificity

Ubiquitous. Ref.1

Domain

The NPF repeat domain is involved in EPS15 binding.

The DPW repeat domain is involved in AP2A2 and clathrin binding.

The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1 By similarity.

Post-translational modification

Ubiquitinated. Ref.8

Phosphorylated on serine and/or threonine residues in mitotic cells. Phosphorylation reduces interaction with REPS2, AP-2 and the membrane fraction. Depolarization of synaptosomes results in dephosphorylation. Ref.3

Sequence similarities

Belongs to the epsin family.

Contains 1 ENTH (epsin N-terminal homology) domain.

Contains 3 UIM (ubiquitin-interacting motif) repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 575575Epsin-1
PRO_0000074515

Regions

Domain12 – 144133ENTH
Repeat183 – 20220UIM 1
Repeat208 – 22720UIM 2
Repeat233 – 25220UIM 3
Repeat274 – 27631
Repeat294 – 29632
Repeat306 – 30833
Repeat319 – 32134
Repeat332 – 33435
Repeat349 – 35136
Repeat367 – 36937
Repeat377 – 37938
Repeat501 – 50331
Repeat517 – 51932
Repeat571 – 57333
Region274 – 3791068 X 3 AA repeats of D-P-W
Region501 – 573733 X 3 AA repeats of N-P-F
Motif401 – 41010[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif
Compositional bias267 – 572306Ala/Gly/Pro-rich

Sites

Binding site81Phosphatidylinositol lipid headgroup
Binding site111Phosphatidylinositol lipid headgroup
Binding site251Phosphatidylinositol lipid headgroup
Binding site301Phosphatidylinositol lipid headgroup
Binding site631Phosphatidylinositol lipid headgroup
Binding site731Phosphatidylinositol lipid headgroup

Amino acid modifications

Modified residue3821Phosphoserine By similarity
Modified residue4181Phosphoserine By similarity
Modified residue4191Phosphoserine By similarity
Modified residue4341Phosphoserine By similarity
Modified residue4531Phosphoserine By similarity
Modified residue4591Phosphothreonine By similarity
Modified residue4691Phosphothreonine By similarity
Modified residue4931Phosphothreonine By similarity

Experimental info

Mutagenesis61L → E, H or Q: Reduces lipid binding. Ref.10
Mutagenesis81R → A: Strongly reduces lipid binding. Ref.7
Mutagenesis631R → L: Strongly reduces lipid binding. Abolishes lipid binding; when associated with L-73. Ref.7 Ref.10
Mutagenesis721R → A: Abolishes ZNF145 binding. Ref.7
Mutagenesis731H → L: Abolishes lipid binding; when associated with L-63. Ref.10
Mutagenesis761K → A: Strongly reduces lipid binding. Ref.7
Mutagenesis1901L → A: Abolishes mono-ubiquitination. Ref.8
Mutagenesis257 – 2593LMD → AAA: Strongly reduces clathrin binding. Ref.6
Mutagenesis260 – 2634LADV → AAAA: Strongly reduces clathrin binding. Ref.6

Secondary structure

....................... 575
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O88339 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: D0B770F3B7AB5DDA

FASTA57560,158
        10         20         30         40         50         60 
MSTSSLRRQM KNIVHNYSEA EIKVREATSN DPWGPSSSLM SEIADLTYNV VAFSEIMSMI 

        70         80         90        100        110        120 
WKRLNDHGKN WRHVYKAMTL MEYLIKTGSE RVSQQCKENM YAVQTLKDFQ YVDRDGKDQG 

       130        140        150        160        170        180 
VNVREKAKQL VALLRDEDRL REERAHALKT KEKLAQTATA SSAAVGSGPP PEAEQAWPQS 

       190        200        210        220        230        240 
SGEEELQLQL ALAMSKEEAD QPPSCGPEDD VQLQLALSLS REEHDKEERI RRGDDLRLQM 

       250        260        270        280        290        300 
AIEESKRETG GKEESSLMDL ADVFTTPAPP QASDPWGGPA SVPTAVPVAA AASDPWGAPA 

       310        320        330        340        350        360 
VPPAADPWGG AAPTPASGDP WRPAAPTGPS VDPWGGTPAP AAGEGPTSDP WGSADGGAPV 

       370        380        390        400        410        420 
SGPPSSDPWA PAPAFSDPWG GSPAKPSSNG TAVGGFDTEP DEFSDFDRLR TALPTSGSST 

       430        440        450        460        470        480 
GELELLAGEV PARSPGAFDM SGVGGSLAES VGSPPPAATP TPTPPTRKTP ESFLGPNAAL 

       490        500        510        520        530        540 
VDLDSLVSRP GPTPPGAKAS NPFLPSGAPA TGPSVTNPFQ PAPPATLTLN QLRLSPVPPV 

       550        560        570 
PGAPPTYISP LGGGPGLPPM MPPGPPAPNT NPFLL 

« Hide

References

[1]"Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis."
Chen H., Fre S., Slepnev V.I., Capua M.R., Takei K., Butler M.H., Di Fiore P.P., De Camilli P.
Nature 394:793-797(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH EPS15; AP2A1 AND AP2A2.
Strain: Wistar.
Tissue: Brain.
[2]"A structural explanation for the binding of multiple ligands by the alpha-adaptin appendage domain."
Owen D.J., Vallis Y., Noble M.E.M., Hunter J.B., Dafforn T.R., Evans P.R., McMahon H.T.
Cell 97:805-815(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AP2A2.
[3]"The interaction of epsin and Eps15 with the clathrin adaptor AP-2 is inhibited by mitotic phosphorylation and enhanced by stimulation-dependent dephosphorylation in nerve terminals."
Chen H., Slepnev V.I., Di Fiore P.P., De Camilli P.
J. Biol. Chem. 274:3257-3260(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH AP-2.
[4]"Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly."
Traub L.M., Downs M.A., Westrich J.L., Fremont D.H.
Proc. Natl. Acad. Sci. U.S.A. 96:8907-8912(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AP2A2.
[5]"The structure and function of the beta 2-adaptin appendage domain."
Owen D.J., Vallis Y., Pearse B.M.F., McMahon H.T., Evans P.R.
EMBO J. 19:4216-4227(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AP2B1.
[6]"Epsin binds to clathrin by associating directly with the clathrin-terminal domain. Evidence for cooperative binding through two discrete sites."
Drake M.T., Downs M.A., Traub L.M.
J. Biol. Chem. 275:6479-6489(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 257-LEU--ASP-259 AND 260-LEU--VAL-263, SUBCELLULAR LOCATION, INTERACTION WITH CLATHRIN HEAVY CHAIN AND AP-2.
[7]"Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis."
Itoh T., Koshiba S., Kigawa T., Kikuchi A., Yokoyama S., Takenawa T.
Science 291:1047-1051(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ZBTB16, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-8; ARG-63; ARG-72 AND LYS-76.
[8]"A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins."
Polo S., Sigismund S., Faretta M., Guidi M., Capua M.R., Bossi G., Chen H., De Camilli P., Di Fiore P.P.
Nature 416:451-455(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LEU-190, UBIQUITINATION.
[9]"Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and Heat repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF)."
Hyman J., Chen H., Di Fiore P.P., De Camilli P., Brunger A.T.
J. Cell Biol. 149:537-546(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 12-160, SUBCELLULAR LOCATION, INTERACTION WITH ZNF145.
[10]"Curvature of clathrin-coated pits driven by epsin."
Ford M.G.J., Mills I.G., Peter B.J., Vallis Y., Praefcke G.J.K., Evans P.R., McMahon H.T.
Nature 419:361-366(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-158 IN COMPLEX WITH INOSITOL-1,4,5-TRIPHOSPHATE, FUNCTION, MUTAGENESIS OF LEU-6; ARG-63 AND HIS-73.
[11]"Accessory protein recruitment motifs in clathrin-mediated endocytosis."
Brett T.J., Traub L.M., Fremont D.H.
Structure 10:797-809(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 375-381 IN COMPLEX WITH AP2A2.
+Additional computationally mapped references.

Web resources

Protein Spotlight

The bubble's bend - Issue 42 of January 2004

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF018261 mRNA. Translation: AAC33823.1.
RefSeqNP_476477.1. NM_057136.1.
UniGeneRn.30007.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EDUX-ray1.80A12-160[»]
1EYHX-ray1.56A15-158[»]
1H0AX-ray1.70A1-158[»]
1KY6X-ray2.00P375-381[»]
DisProtDP00251.
ProteinModelPortalO88339.
SMRO88339. Positions 1-158.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid250724. 16 interactions.
IntActO88339. 2 interactions.
MINTMINT-101104.
STRING10116.ENSRNOP00000021286.

PTM databases

PhosphoSiteO88339.

Proteomic databases

PaxDbO88339.
PRIDEO88339.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000021286; ENSRNOP00000021286; ENSRNOG00000015753.
GeneID117277.
KEGGrno:117277.
UCSCRGD:619772. rat.

Organism-specific databases

CTD29924.
RGD619772. Epn1.

Phylogenomic databases

eggNOGNOG263730.
GeneTreeENSGT00550000074611.
HOGENOMHOG000008298.
HOVERGENHBG006690.
InParanoidO88339.
KOK12471.
OMADPWGGTQ.
OrthoDBEOG7F511Z.
PhylomeDBO88339.

Gene expression databases

GenevestigatorO88339.

Family and domain databases

Gene3D1.25.40.90. 1 hit.
InterProIPR008942. ENTH_VHS.
IPR013809. Epsin-like_N.
IPR001026. Epsin_dom_N.
IPR003903. Ubiquitin-int_motif.
[Graphical view]
PfamPF01417. ENTH. 1 hit.
PF02809. UIM. 2 hits.
[Graphical view]
SMARTSM00273. ENTH. 1 hit.
SM00726. UIM. 3 hits.
[Graphical view]
SUPFAMSSF48464. SSF48464. 1 hit.
PROSITEPS50942. ENTH. 1 hit.
PS50330. UIM. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO88339.
NextBio620217.
PROO88339.

Entry information

Entry nameEPN1_RAT
AccessionPrimary (citable) accession number: O88339
Entry history
Integrated into UniProtKB/Swiss-Prot: January 16, 2004
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references