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Database: UniProt
Entry: EPN1_RAT
LinkDB: EPN1_RAT
Original site: EPN1_RAT 
ID   EPN1_RAT                Reviewed;         575 AA.
AC   O88339;
DT   16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   31-JUL-2019, entry version 163.
DE   RecName: Full=Epsin-1;
DE   AltName: Full=EPS-15-interacting protein 1;
GN   Name=Epn1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND INTERACTION WITH EPS15; AP2A1 AND AP2A2.
RC   STRAIN=Wistar; TISSUE=Brain;
RX   PubMed=9723620; DOI=10.1038/29555;
RA   Chen H., Fre S., Slepnev V.I., Capua M.R., Takei K., Butler M.H.,
RA   Di Fiore P.P., De Camilli P.;
RT   "Epsin is an EH-domain-binding protein implicated in clathrin-mediated
RT   endocytosis.";
RL   Nature 394:793-797(1998).
RN   [2]
RP   INTERACTION WITH AP2A2.
RX   PubMed=10380931; DOI=10.1016/S0092-8674(00)80791-6;
RA   Owen D.J., Vallis Y., Noble M.E.M., Hunter J.B., Dafforn T.R.,
RA   Evans P.R., McMahon H.T.;
RT   "A structural explanation for the binding of multiple ligands by the
RT   alpha-adaptin appendage domain.";
RL   Cell 97:805-815(1999).
RN   [3]
RP   PHOSPHORYLATION, AND INTERACTION WITH AP-2.
RX   PubMed=9920862; DOI=10.1074/jbc.274.6.3257;
RA   Chen H., Slepnev V.I., Di Fiore P.P., De Camilli P.;
RT   "The interaction of epsin and Eps15 with the clathrin adaptor AP-2 is
RT   inhibited by mitotic phosphorylation and enhanced by stimulation-
RT   dependent dephosphorylation in nerve terminals.";
RL   J. Biol. Chem. 274:3257-3260(1999).
RN   [4]
RP   INTERACTION WITH AP2A2.
RX   PubMed=10430869; DOI=10.1073/pnas.96.16.8907;
RA   Traub L.M., Downs M.A., Westrich J.L., Fremont D.H.;
RT   "Crystal structure of the alpha appendage of AP-2 reveals a
RT   recruitment platform for clathrin-coat assembly.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:8907-8912(1999).
RN   [5]
RP   INTERACTION WITH AP2B1.
RX   PubMed=10944104; DOI=10.1093/emboj/19.16.4216;
RA   Owen D.J., Vallis Y., Pearse B.M.F., McMahon H.T., Evans P.R.;
RT   "The structure and function of the beta 2-adaptin appendage domain.";
RL   EMBO J. 19:4216-4227(2000).
RN   [6]
RP   MUTAGENESIS OF 257-LEU--ASP-259 AND 260-LEU--VAL-263, SUBCELLULAR
RP   LOCATION, AND INTERACTION WITH CLATHRIN HEAVY CHAIN AND AP-2.
RX   PubMed=10692452; DOI=10.1074/jbc.275.9.6479;
RA   Drake M.T., Downs M.A., Traub L.M.;
RT   "Epsin binds to clathrin by associating directly with the clathrin-
RT   terminal domain. Evidence for cooperative binding through two discrete
RT   sites.";
RL   J. Biol. Chem. 275:6479-6489(2000).
RN   [7]
RP   FUNCTION, INTERACTION WITH ZBTB16, SUBCELLULAR LOCATION, AND
RP   MUTAGENESIS OF ARG-8; ARG-63; ARG-72 AND LYS-76.
RX   PubMed=11161217; DOI=10.1126/science.291.5506.1047;
RA   Itoh T., Koshiba S., Kigawa T., Kikuchi A., Yokoyama S., Takenawa T.;
RT   "Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate
RT   binding and endocytosis.";
RL   Science 291:1047-1051(2001).
RN   [8]
RP   MUTAGENESIS OF LEU-190, AND UBIQUITINATION.
RX   PubMed=11919637; DOI=10.1038/416451a;
RA   Polo S., Sigismund S., Faretta M., Guidi M., Capua M.R., Bossi G.,
RA   Chen H., De Camilli P., Di Fiore P.P.;
RT   "A single motif responsible for ubiquitin recognition and
RT   monoubiquitination in endocytic proteins.";
RL   Nature 416:451-455(2002).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453 AND THR-469, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
RA   Lundby C., Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14
RT   different rat organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 12-160, SUBCELLULAR LOCATION,
RP   AND INTERACTION WITH ZNF145.
RX   PubMed=10791968; DOI=10.1083/jcb.149.3.537;
RA   Hyman J., Chen H., Di Fiore P.P., De Camilli P., Brunger A.T.;
RT   "Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor
RT   NH(2)-terminal homology (ENTH) domain, structurally similar to
RT   Armadillo and Heat repeats, interacts with the transcription factor
RT   promyelocytic leukemia Zn(2)+ finger protein (PLZF).";
RL   J. Cell Biol. 149:537-546(2000).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-158 IN COMPLEX WITH
RP   INOSITOL-1,4,5-TRIPHOSPHATE, FUNCTION, AND MUTAGENESIS OF LEU-6;
RP   ARG-63 AND HIS-73.
RX   PubMed=12353027; DOI=10.1038/nature01020;
RA   Ford M.G.J., Mills I.G., Peter B.J., Vallis Y., Praefcke G.J.K.,
RA   Evans P.R., McMahon H.T.;
RT   "Curvature of clathrin-coated pits driven by epsin.";
RL   Nature 419:361-366(2002).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 375-381 IN COMPLEX WITH
RP   AP2A2.
RX   PubMed=12057195; DOI=10.1016/S0969-2126(02)00784-0;
RA   Brett T.J., Traub L.M., Fremont D.H.;
RT   "Accessory protein recruitment motifs in clathrin-mediated
RT   endocytosis.";
RL   Structure 10:797-809(2002).
CC   -!- FUNCTION: Binds to membranes enriched in phosphatidylinositol 4,5-
CC       bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and
CC       facilitates the formation of clathrin-coated invaginations.
CC       Regulates receptor-mediated endocytosis.
CC       {ECO:0000269|PubMed:11161217, ECO:0000269|PubMed:12353027,
CC       ECO:0000269|PubMed:9723620}.
CC   -!- SUBUNIT: Monomer. Binds REPS2 and ITSN1 (By similarity). Binds
CC       EPS15, clathrin, ZBTB16/ZNF145, AP2A1 and AP2A2. Binds
CC       ubiquitinated proteins. Interacts with RALBP1 in a complex also
CC       containing NUMB and TFAP2A during interphase and mitosis.
CC       Interacts with AP2B1. Interacts with UBQLN2 (By similarity).
CC       {ECO:0000250|UniProtKB:Q80VP1, ECO:0000250|UniProtKB:Q9Y6I3,
CC       ECO:0000269|PubMed:10380931, ECO:0000269|PubMed:10430869,
CC       ECO:0000269|PubMed:10692452, ECO:0000269|PubMed:10791968,
CC       ECO:0000269|PubMed:10944104, ECO:0000269|PubMed:11161217,
CC       ECO:0000269|PubMed:12057195, ECO:0000269|PubMed:12353027,
CC       ECO:0000269|PubMed:9723620, ECO:0000269|PubMed:9920862}.
CC   -!- INTERACTION:
CC       P39083:RGA1 (xeno); NbExp=2; IntAct=EBI-7066728, EBI-15044;
CC       Q06407:RGA2 (xeno); NbExp=2; IntAct=EBI-7066728, EBI-15060;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral
CC       membrane protein. Nucleus. Membrane, clathrin-coated pit.
CC       Note=Associated with the cytoplasmic membrane at sites where
CC       clathrin-coated pits are forming. Colocalizes with clathrin and
CC       AP-2 in a punctate pattern on the plasma membrane. Colocalizes
CC       with clathrin at the Golgi complex. Detected in presynaptic nerve
CC       terminals and in synaptosomes. May shuttle to the nucleus when
CC       associated with ZBTB16/ZNF145.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9723620}.
CC   -!- DOMAIN: The NPF repeat domain is involved in EPS15 binding.
CC   -!- DOMAIN: The DPW repeat domain is involved in AP2A2 and clathrin
CC       binding.
CC   -!- DOMAIN: The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates
CC       interaction the AP-2 complex subunit AP2B1. {ECO:0000250}.
CC   -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:11919637}.
CC   -!- PTM: Phosphorylated on serine and/or threonine residues in mitotic
CC       cells. Phosphorylation reduces interaction with REPS2, AP-2 and
CC       the membrane fraction. Depolarization of synaptosomes results in
CC       dephosphorylation. {ECO:0000269|PubMed:9920862}.
CC   -!- SIMILARITY: Belongs to the epsin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=The bubble's bend
CC       - Issue 42 of January 2004;
CC       URL="https://web.expasy.org/spotlight/back_issues/042";
DR   EMBL; AF018261; AAC33823.1; -; mRNA.
DR   RefSeq; NP_476477.1; NM_057136.1.
DR   PDB; 1EDU; X-ray; 1.80 A; A=12-160.
DR   PDB; 1EYH; X-ray; 1.56 A; A=15-158.
DR   PDB; 1H0A; X-ray; 1.70 A; A=1-158.
DR   PDB; 1KY6; X-ray; 2.00 A; P=375-381.
DR   PDBsum; 1EDU; -.
DR   PDBsum; 1EYH; -.
DR   PDBsum; 1H0A; -.
DR   PDBsum; 1KY6; -.
DR   SMR; O88339; -.
DR   BioGrid; 250724; 16.
DR   CORUM; O88339; -.
DR   DIP; DIP-40738N; -.
DR   ELM; O88339; -.
DR   IntAct; O88339; 4.
DR   MINT; O88339; -.
DR   STRING; 10116.ENSRNOP00000021286; -.
DR   iPTMnet; O88339; -.
DR   PhosphoSitePlus; O88339; -.
DR   jPOST; O88339; -.
DR   PaxDb; O88339; -.
DR   PeptideAtlas; O88339; -.
DR   PRIDE; O88339; -.
DR   GeneID; 117277; -.
DR   KEGG; rno:117277; -.
DR   UCSC; RGD:619772; rat.
DR   CTD; 29924; -.
DR   RGD; 619772; Epn1.
DR   eggNOG; KOG2056; Eukaryota.
DR   eggNOG; ENOG410XSM0; LUCA.
DR   HOGENOM; HOG000008298; -.
DR   InParanoid; O88339; -.
DR   KO; K12471; -.
DR   OrthoDB; 1263849at2759; -.
DR   PhylomeDB; O88339; -.
DR   Reactome; R-RNO-182971; EGFR downregulation.
DR   Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR   EvolutionaryTrace; O88339; -.
DR   PRO; PR:O88339; -.
DR   Proteomes; UP000002494; Unplaced.
DR   Genevisible; O88339; RN.
DR   GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; IDA:CAFA.
DR   GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0098890; C:extrinsic component of postsynaptic membrane; IDA:BHF-UCL.
DR   GO; GO:0098888; C:extrinsic component of presynaptic membrane; IDA:BHF-UCL.
DR   GO; GO:0005634; C:nucleus; IDA:RGD.
DR   GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR   GO; GO:0098793; C:presynapse; IDA:SynGO.
DR   GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR   GO; GO:0043195; C:terminal bouton; HDA:ParkinsonsUK-UCL.
DR   GO; GO:0035615; F:clathrin adaptor activity; IMP:CAFA.
DR   GO; GO:0044325; F:ion channel binding; IPI:RGD.
DR   GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR   GO; GO:0008134; F:transcription factor binding; IPI:RGD.
DR   GO; GO:0006897; P:endocytosis; IDA:RGD.
DR   GO; GO:1905445; P:positive regulation of clathrin coat assembly; IMP:CAFA.
DR   DisProt; DP00251; -.
DR   Gene3D; 1.25.40.90; -; 1.
DR   InterPro; IPR013809; ENTH.
DR   InterPro; IPR008942; ENTH_VHS.
DR   InterPro; IPR003903; UIM_dom.
DR   Pfam; PF01417; ENTH; 1.
DR   SMART; SM00273; ENTH; 1.
DR   SMART; SM00726; UIM; 3.
DR   SUPFAM; SSF48464; SSF48464; 1.
DR   PROSITE; PS50942; ENTH; 1.
DR   PROSITE; PS50330; UIM; 3.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Coated pit; Complete proteome; Cytoplasm;
KW   Endocytosis; Lipid-binding; Membrane; Methylation; Nucleus;
KW   Phosphoprotein; Reference proteome; Repeat; Ubl conjugation.
FT   CHAIN         1    575       Epsin-1.
FT                                /FTId=PRO_0000074515.
FT   DOMAIN       12    144       ENTH. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00243}.
FT   DOMAIN      183    202       UIM 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00213}.
FT   DOMAIN      208    227       UIM 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00213}.
FT   DOMAIN      233    252       UIM 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00213}.
FT   REPEAT      274    276       1.
FT   REPEAT      294    296       2.
FT   REPEAT      306    308       3.
FT   REPEAT      319    321       4.
FT   REPEAT      332    334       5.
FT   REPEAT      349    351       6.
FT   REPEAT      367    369       7.
FT   REPEAT      377    379       8.
FT   REPEAT      501    503       1.
FT   REPEAT      517    519       2.
FT   REPEAT      571    573       3.
FT   REGION      274    379       8 X 3 AA repeats of D-P-W.
FT   REGION      501    573       3 X 3 AA repeats of N-P-F.
FT   MOTIF       401    410       [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif.
FT   COMPBIAS    267    572       Ala/Gly/Pro-rich.
FT   BINDING       8      8       Phosphatidylinositol lipid headgroup.
FT   BINDING      11     11       Phosphatidylinositol lipid headgroup.
FT   BINDING      25     25       Phosphatidylinositol lipid headgroup.
FT   BINDING      30     30       Phosphatidylinositol lipid headgroup.
FT   BINDING      63     63       Phosphatidylinositol lipid headgroup.
FT   BINDING      73     73       Phosphatidylinositol lipid headgroup.
FT   MOD_RES     382    382       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q9Y6I3}.
FT   MOD_RES     418    418       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q9Y6I3}.
FT   MOD_RES     419    419       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q9Y6I3}.
FT   MOD_RES     420    420       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q80VP1}.
FT   MOD_RES     434    434       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q9Y6I3}.
FT   MOD_RES     446    446       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q9Y6I3}.
FT   MOD_RES     453    453       Phosphoserine.
FT                                {ECO:0000244|PubMed:22673903}.
FT   MOD_RES     459    459       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q9Y6I3}.
FT   MOD_RES     463    463       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q9Y6I3}.
FT   MOD_RES     469    469       Phosphothreonine.
FT                                {ECO:0000244|PubMed:22673903}.
FT   MOD_RES     472    472       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q80VP1}.
FT   MOD_RES     493    493       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q9Y6I3}.
FT   MOD_RES     533    533       Omega-N-methylarginine.
FT                                {ECO:0000250|UniProtKB:Q80VP1}.
FT   MUTAGEN       6      6       L->E,H,Q: Reduces lipid binding.
FT                                {ECO:0000269|PubMed:12353027}.
FT   MUTAGEN       8      8       R->A: Strongly reduces lipid binding.
FT                                {ECO:0000269|PubMed:11161217}.
FT   MUTAGEN      63     63       R->L: Strongly reduces lipid binding.
FT                                Abolishes lipid binding; when associated
FT                                with L-73. {ECO:0000269|PubMed:11161217,
FT                                ECO:0000269|PubMed:12353027}.
FT   MUTAGEN      72     72       R->A: Abolishes ZNF145 binding.
FT                                {ECO:0000269|PubMed:11161217}.
FT   MUTAGEN      73     73       H->L: Abolishes lipid binding; when
FT                                associated with L-63.
FT                                {ECO:0000269|PubMed:12353027}.
FT   MUTAGEN      76     76       K->A: Strongly reduces lipid binding.
FT                                {ECO:0000269|PubMed:11161217}.
FT   MUTAGEN     190    190       L->A: Abolishes mono-ubiquitination.
FT                                {ECO:0000269|PubMed:11919637}.
FT   MUTAGEN     257    259       LMD->AAA: Strongly reduces clathrin
FT                                binding. {ECO:0000269|PubMed:10692452}.
FT   MUTAGEN     260    263       LADV->AAAA: Strongly reduces clathrin
FT                                binding. {ECO:0000269|PubMed:10692452}.
FT   HELIX         2     15       {ECO:0000244|PDB:1H0A}.
FT   HELIX        19     27       {ECO:0000244|PDB:1EYH}.
FT   STRAND       30     33       {ECO:0000244|PDB:1EYH}.
FT   HELIX        37     46       {ECO:0000244|PDB:1EYH}.
FT   HELIX        50     64       {ECO:0000244|PDB:1EYH}.
FT   HELIX        68     70       {ECO:0000244|PDB:1EYH}.
FT   HELIX        71     87       {ECO:0000244|PDB:1EYH}.
FT   HELIX        90     98       {ECO:0000244|PDB:1EYH}.
FT   HELIX       100    104       {ECO:0000244|PDB:1EYH}.
FT   HELIX       105    108       {ECO:0000244|PDB:1EYH}.
FT   HELIX       120    135       {ECO:0000244|PDB:1EYH}.
FT   HELIX       137    155       {ECO:0000244|PDB:1EYH}.
SQ   SEQUENCE   575 AA;  60158 MW;  D0B770F3B7AB5DDA CRC64;
     MSTSSLRRQM KNIVHNYSEA EIKVREATSN DPWGPSSSLM SEIADLTYNV VAFSEIMSMI
     WKRLNDHGKN WRHVYKAMTL MEYLIKTGSE RVSQQCKENM YAVQTLKDFQ YVDRDGKDQG
     VNVREKAKQL VALLRDEDRL REERAHALKT KEKLAQTATA SSAAVGSGPP PEAEQAWPQS
     SGEEELQLQL ALAMSKEEAD QPPSCGPEDD VQLQLALSLS REEHDKEERI RRGDDLRLQM
     AIEESKRETG GKEESSLMDL ADVFTTPAPP QASDPWGGPA SVPTAVPVAA AASDPWGAPA
     VPPAADPWGG AAPTPASGDP WRPAAPTGPS VDPWGGTPAP AAGEGPTSDP WGSADGGAPV
     SGPPSSDPWA PAPAFSDPWG GSPAKPSSNG TAVGGFDTEP DEFSDFDRLR TALPTSGSST
     GELELLAGEV PARSPGAFDM SGVGGSLAES VGSPPPAATP TPTPPTRKTP ESFLGPNAAL
     VDLDSLVSRP GPTPPGAKAS NPFLPSGAPA TGPSVTNPFQ PAPPATLTLN QLRLSPVPPV
     PGAPPTYISP LGGGPGLPPM MPPGPPAPNT NPFLL
//
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