EPN1_HUMAN
ID EPN1_HUMAN Reviewed; 576 AA.
AC Q9Y6I3; Q86ST3; Q9HA18;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Epsin-1;
DE AltName: Full=EH domain-binding mitotic phosphoprotein;
DE AltName: Full=EPS-15-interacting protein 1;
GN Name=EPN1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND INTERACTION WITH
RP REPS2.
RC TISSUE=Brain;
RX PubMed=10557078; DOI=10.1038/sj.onc.1202974;
RA Morinaka K., Koyama S., Nakashima S., Hinoi T., Okawa K., Iwamatsu A.,
RA Kikuchi A.;
RT "Epsin binds to the EH domain of POB1 and regulates receptor-mediated
RT endocytosis.";
RL Oncogene 18:5915-5922(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION AT SER-382, MUTAGENESIS OF SER-382, AND INTERACTION WITH
RP REPS2; EPS15 AND AP-2 ALPHA SUBUNIT.
RX PubMed=10764745; DOI=10.1074/jbc.m000521200;
RA Kariya K., Koyama S., Nakashima S., Oshiro T., Morinaka K., Kikuchi A.;
RT "Regulation of complex formation of POB1/epsin/adaptor protein complex 2 by
RT mitotic phosphorylation.";
RL J. Biol. Chem. 275:18399-18406(2000).
RN [6]
RP FUNCTION, AND INTERACTION WITH EPS15 AND REPS2.
RX PubMed=10393179; DOI=10.1093/emboj/18.13.3629;
RA Nakashima S., Morinaka K., Koyama S., Ikeda M., Kishida M., Okawa K.,
RA Iwamatsu A., Kishida S., Kikuchi A.;
RT "Small G protein Ral and its downstream molecules regulate endocytosis of
RT EGF and insulin receptors.";
RL EMBO J. 18:3629-3642(1999).
RN [7]
RP INTERACTION WITH RALBP1.
RX PubMed=12775724; DOI=10.1074/jbc.m302191200;
RA Rosse C., L'Hoste S., Offner N., Picard A., Camonis J.;
RT "RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to
RT phosphorylate epsin during the switch off of endocytosis in mitosis.";
RL J. Biol. Chem. 278:30597-30604(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-494, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP INTERACTION WITH AP2B1, AND MUTAGENESIS OF PHE-404.
RX PubMed=16516836; DOI=10.1016/j.devcel.2006.01.016;
RA Edeling M.A., Mishra S.K., Keyel P.A., Steinhauser A.L., Collins B.M.,
RA Roth R., Heuser J.E., Owen D.J., Traub L.M.;
RT "Molecular switches involving the AP-2 beta2 appendage regulate endocytic
RT cargo selection and clathrin coat assembly.";
RL Dev. Cell 10:329-342(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-454 AND THR-460, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [12]
RP INTERACTION WITH UBQLN2.
RX PubMed=18199683; DOI=10.1091/mbc.e07-08-0775;
RA N'Diaye E.N., Hanyaloglu A.C., Kajihara K.K., Puthenveedu M.A., Wu P.,
RA von Zastrow M., Brown E.J.;
RT "The ubiquitin-like protein PLIC-2 is a negative regulator of G protein-
RT coupled receptor endocytosis.";
RL Mol. Biol. Cell 19:1252-1260(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-454; THR-460 AND
RP THR-494, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419; SER-420; SER-435;
RP SER-454; THR-460 AND THR-470, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-454; THR-460 AND
RP THR-494, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-447 AND SER-454, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419; SER-420; SER-435;
RP SER-447; SER-454 AND THR-464, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
RP STRUCTURE BY NMR OF 1-144.
RX PubMed=12836669; DOI=10.1023/a:1011397007366;
RA Koshiba S., Kigawa T., Kikuchi A., Yokoyama S.;
RT "Solution structure of the epsin N-terminal homology (ENTH) domain of human
RT epsin.";
RL J. Struct. Funct. Genomics 2:1-8(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 (By
CC similarity). Regulates receptor-mediated endocytosis (PubMed:10557078,
CC PubMed:10393179). {ECO:0000250|UniProtKB:O88339,
CC ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:10557078}.
CC -!- SUBUNIT: Monomer. Binds clathrin, ZBTB16/ZNF145 and ITSN1 (By
CC similarity). Binds ubiquitinated proteins (By similarity). Binds AP2A1
CC and AP2A2. Interacts with RALBP1 in a complex also containing NUMB and
CC TFAP2A during interphase and mitosis. Interacts with AP2B1. Interacts
CC with UBQLN2. Interacts with REPS2; the interaction is direct
CC (PubMed:10557078, PubMed:10764745, PubMed:10393179). Interacts with
CC EPS15; the interaction is direct (PubMed:10764745, PubMed:10393179).
CC {ECO:0000250|UniProtKB:O88339, ECO:0000250|UniProtKB:Q80VP1,
CC ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:10557078,
CC ECO:0000269|PubMed:10764745, ECO:0000269|PubMed:12775724,
CC ECO:0000269|PubMed:16516836, ECO:0000269|PubMed:18199683}.
CC -!- INTERACTION:
CC Q9Y6I3; Q15038: DAZAP2; NbExp=3; IntAct=EBI-713198, EBI-724310;
CC Q9Y6I3; P42566: EPS15; NbExp=2; IntAct=EBI-713198, EBI-396684;
CC Q9Y6I3; Q15884: FAM189A2; NbExp=5; IntAct=EBI-713198, EBI-8636612;
CC Q9Y6I3; Q96CS7: PLEKHB2; NbExp=3; IntAct=EBI-713198, EBI-373552;
CC Q9Y6I3-3; Q15038: DAZAP2; NbExp=3; IntAct=EBI-12026538, EBI-724310;
CC Q9Y6I3-3; Q99732: LITAF; NbExp=3; IntAct=EBI-12026538, EBI-725647;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus
CC {ECO:0000250}. Membrane, clathrin-coated pit {ECO:0000250}.
CC Note=Associated with the cytoplasmic membrane at sites where clathrin-
CC coated pits are forming. Colocalizes with clathrin and AP-2 in a
CC punctate pattern on the plasma membrane. Detected in presynaptic nerve
CC terminals and in Golgi stacks. May shuttle to the nucleus when
CC associated with ZBTB16/ZNF145 (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y6I3-2; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y6I3-1; Sequence=VSP_041010, VSP_041011;
CC Name=3;
CC IsoId=Q9Y6I3-3; Sequence=VSP_041011, VSP_041012;
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 interaction
CC with the AP-2 complex subunit AP2B1. {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine and/or threonine residues in mitotic
CC cells. Phosphorylation reduces interaction with REPS2, AP-2 and the
CC membrane fraction. Depolarization of synaptosomes results in
CC dephosphorylation. {ECO:0000269|PubMed:10764745}.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be due to a competing donor splice
CC site. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the epsin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION: [Isoform 2]:
CC Sequence=AAD38326.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The bubble's bend - Issue 42
CC of January 2004;
CC URL="https://web.expasy.org/spotlight/back_issues/042";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF073727; AAD38326.1; ALT_FRAME; mRNA.
DR EMBL; AK022454; BAB14041.1; -; mRNA.
DR EMBL; AC008735; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010525; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC044651; AAH44651.1; -; mRNA.
DR CCDS; CCDS46198.1; -. [Q9Y6I3-1]
DR CCDS; CCDS46199.1; -. [Q9Y6I3-2]
DR CCDS; CCDS46200.1; -. [Q9Y6I3-3]
DR RefSeq; NP_001123543.1; NM_001130071.1. [Q9Y6I3-1]
DR RefSeq; NP_001123544.1; NM_001130072.1. [Q9Y6I3-2]
DR RefSeq; NP_037465.2; NM_013333.3. [Q9Y6I3-3]
DR RefSeq; XP_005258886.1; XM_005258829.2.
DR RefSeq; XP_011525183.1; XM_011526881.1.
DR RefSeq; XP_016882211.1; XM_017026722.1.
DR PDB; 1INZ; NMR; -; A=1-144.
DR PDB; 1KYD; X-ray; 2.00 A; P=366-370.
DR PDBsum; 1INZ; -.
DR PDBsum; 1KYD; -.
DR AlphaFoldDB; Q9Y6I3; -.
DR BMRB; Q9Y6I3; -.
DR SMR; Q9Y6I3; -.
DR BioGRID; 118965; 99.
DR CORUM; Q9Y6I3; -.
DR ELM; Q9Y6I3; -.
DR IntAct; Q9Y6I3; 42.
DR MINT; Q9Y6I3; -.
DR STRING; 9606.ENSP00000406209; -.
DR BindingDB; Q9Y6I3; -.
DR ChEMBL; CHEMBL3259465; -.
DR DrugBank; DB03316; 1,4-Dioxane.
DR DrugBank; DB03401; 1D-myo-inositol 1,4,5-trisphosphate.
DR MoonDB; Q9Y6I3; Curated.
DR GlyGen; Q9Y6I3; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q9Y6I3; -.
DR MetOSite; Q9Y6I3; -.
DR PhosphoSitePlus; Q9Y6I3; -.
DR BioMuta; EPN1; -.
DR DMDM; 332278179; -.
DR EPD; Q9Y6I3; -.
DR jPOST; Q9Y6I3; -.
DR MassIVE; Q9Y6I3; -.
DR MaxQB; Q9Y6I3; -.
DR PeptideAtlas; Q9Y6I3; -.
DR PRIDE; Q9Y6I3; -.
DR ProteomicsDB; 86689; -. [Q9Y6I3-2]
DR ProteomicsDB; 86690; -. [Q9Y6I3-1]
DR ProteomicsDB; 86691; -. [Q9Y6I3-3]
DR Antibodypedia; 4051; 221 antibodies from 30 providers.
DR DNASU; 29924; -.
DR Ensembl; ENST00000085079.11; ENSP00000085079.6; ENSG00000063245.15. [Q9Y6I3-3]
DR Ensembl; ENST00000270460.11; ENSP00000270460.6; ENSG00000063245.15. [Q9Y6I3-2]
DR Ensembl; ENST00000411543.6; ENSP00000406209.1; ENSG00000063245.15. [Q9Y6I3-1]
DR GeneID; 29924; -.
DR KEGG; hsa:29924; -.
DR MANE-Select; ENST00000270460.11; ENSP00000270460.6; NM_001130072.2; NP_001123544.1.
DR UCSC; uc002qlv.4; human. [Q9Y6I3-2]
DR CTD; 29924; -.
DR DisGeNET; 29924; -.
DR GeneCards; EPN1; -.
DR HGNC; HGNC:21604; EPN1.
DR HPA; ENSG00000063245; Low tissue specificity.
DR MIM; 607262; gene.
DR neXtProt; NX_Q9Y6I3; -.
DR OpenTargets; ENSG00000063245; -.
DR PharmGKB; PA134860916; -.
DR VEuPathDB; HostDB:ENSG00000063245; -.
DR eggNOG; KOG2056; Eukaryota.
DR GeneTree; ENSGT00940000160411; -.
DR HOGENOM; CLU_012678_4_2_1; -.
DR InParanoid; Q9Y6I3; -.
DR OMA; CEKADEM; -.
DR OrthoDB; 1263849at2759; -.
DR TreeFam; TF313361; -.
DR PathwayCommons; Q9Y6I3; -.
DR Reactome; R-HSA-182971; EGFR downregulation.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q9Y6I3; -.
DR SIGNOR; Q9Y6I3; -.
DR BioGRID-ORCS; 29924; 30 hits in 1085 CRISPR screens.
DR ChiTaRS; EPN1; human.
DR EvolutionaryTrace; Q9Y6I3; -.
DR GeneWiki; EPN1; -.
DR GenomeRNAi; 29924; -.
DR Pharos; Q9Y6I3; Tbio.
DR PRO; PR:Q9Y6I3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9Y6I3; protein.
DR Bgee; ENSG00000063245; Expressed in apex of heart and 183 other tissues.
DR ExpressionAtlas; Q9Y6I3; baseline and differential.
DR Genevisible; Q9Y6I3; HS.
DR GO; GO:0030125; C:clathrin vesicle coat; IBA:GO_Central.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
DR GO; GO:0005543; F:phospholipid binding; IBA:GO_Central.
DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; IGI:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR DisProt; DP02930; -.
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 Pfam; PF02809; UIM; 3.
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; Alternative splicing; Cell membrane; Coated pit; Cytoplasm;
KW Endocytosis; Lipid-binding; Membrane; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..576
FT /note="Epsin-1"
FT /id="PRO_0000074513"
FT DOMAIN 12..144
FT /note="ENTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00243"
FT DOMAIN 183..202
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 208..227
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 233..252
FT /note="UIM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT REPEAT 274..276
FT /note="1"
FT REPEAT 294..296
FT /note="2"
FT REPEAT 306..308
FT /note="3"
FT REPEAT 319..321
FT /note="4"
FT REPEAT 332..334
FT /note="5"
FT REPEAT 349..351
FT /note="6"
FT REPEAT 367..369
FT /note="7"
FT REPEAT 377..379
FT /note="8"
FT REPEAT 502..504
FT /note="1"
FT REPEAT 518..520
FT /note="2"
FT REPEAT 572..574
FT /note="3"
FT REGION 149..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 265..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 274..379
FT /note="8 X 3 AA repeats of [ED]-P-W"
FT REGION 448..576
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 502..574
FT /note="3 X 3 AA repeats of N-P-F"
FT MOTIF 402..411
FT /note="[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif"
FT COMPBIAS 293..322
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 456..470
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 538..576
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 8
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250"
FT BINDING 11
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250"
FT BINDING 25
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250"
FT BINDING 30
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250"
FT BINDING 63
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250"
FT BINDING 73
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250"
FT MOD_RES 382
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:10764745"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 420
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 460
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 464
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 470
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80VP1"
FT MOD_RES 494
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231"
FT MOD_RES 534
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q80VP1"
FT VAR_SEQ 1
FT /note="M -> MGDQSWLWNQAAPGVRSPVFACSVEKGNVPLVLSEHLAHSRDPGSGA
FT VRFLISPEPWASAILGTSGLLASPVLPAALDAVTCQHLPQPSSGSRPISPRIGALCPLL
FT LQPGTM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10557078"
FT /id="VSP_041010"
FT VAR_SEQ 202..226
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10557078,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_041011"
FT VAR_SEQ 393
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041012"
FT MUTAGEN 382
FT /note="S->A: Abolishes phosphorylation by CDK1."
FT /evidence="ECO:0000269|PubMed:10764745"
FT MUTAGEN 382
FT /note="S->D: Abolishes phosphorylation by CDK1 and reduces
FT REPS2 binding."
FT /evidence="ECO:0000269|PubMed:10764745"
FT MUTAGEN 404
FT /note="F->A: Reduces interaction with AP2B1."
FT /evidence="ECO:0000269|PubMed:16516836"
FT HELIX 20..27
FT /evidence="ECO:0007829|PDB:1INZ"
FT HELIX 39..47
FT /evidence="ECO:0007829|PDB:1INZ"
FT HELIX 51..62
FT /evidence="ECO:0007829|PDB:1INZ"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:1INZ"
FT HELIX 72..86
FT /evidence="ECO:0007829|PDB:1INZ"
FT HELIX 90..98
FT /evidence="ECO:0007829|PDB:1INZ"
FT HELIX 100..108
FT /evidence="ECO:0007829|PDB:1INZ"
FT HELIX 121..134
FT /evidence="ECO:0007829|PDB:1INZ"
SQ SEQUENCE 576 AA; 60293 MW; 68DD433F3168E975 CRC64;
MSTSSLRRQM KNIVHNYSEA EIKVREATSN DPWGPSSSLM SEIADLTYNV VAFSEIMSMI
WKRLNDHGKN WRHVYKAMTL MEYLIKTGSE RVSQQCKENM YAVQTLKDFQ YVDRDGKDQG
VNVREKAKQL VALLRDEDRL REERAHALKT KEKLAQTATA SSAAVGSGPP PEAEQAWPQS
SGEEELQLQL ALAMSKEEAD QPPSCGPEDD AQLQLALSLS REEHDKEERI RRGDDLRLQM
AIEESKRETG GKEESSLMDL ADVFTAPAPA PTTDPWGGPA PMAAAVPTAA PTSDPWGGPP
VPPAADPWGG PAPTPASGDP WRPAAPAGPS VDPWGGTPAP AAGEGPTPDP WGSSDGGVPV
SGPSASDPWT PAPAFSDPWG GSPAKPSTNG TTAAGGFDTE PDEFSDFDRL RTALPTSGSS
AGELELLAGE VPARSPGAFD MSGVRGSLAE AVGSPPPAAT PTPTPPTRKT PESFLGPNAA
LVDLDSLVSR PGPTPPGAKA SNPFLPGGGP ATGPSVTNPF QPAPPATLTL NQLRLSPVPP
VPGAPPTYIS PLGGGPGLPP MMPPGPPAPN TNPFLL
