Full text data of EPN1
EPN1
[Confidence: low (only semi-automatic identification from reviews)]
Epsin-1 (EH domain-binding mitotic phosphoprotein; EPS-15-interacting protein 1)
Epsin-1 (EH domain-binding mitotic phosphoprotein; EPS-15-interacting protein 1)
UniProt
Q9Y6I3
ID EPN1_HUMAN Reviewed; 576 AA.
AC Q9Y6I3; Q86ST3; Q9HA18;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-MAY-2011, sequence version 2.
DT 22-JAN-2014, entry version 129.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA 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
RT project: 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
RP WITH 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.,
RA Kikuchi A.;
RT "Regulation of complex formation of POB1/epsin/adaptor protein complex
RT 2 by mitotic phosphorylation.";
RL J. Biol. Chem. 275:18399-18406(2000).
RN [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-494, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
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
RT endocytic cargo selection and clathrin coat assembly.";
RL Dev. Cell 10:329-342(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-454 AND THR-460, AND
RP MASS SPECTROMETRY.
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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [10]
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
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-454; THR-460
RP AND THR-494, AND MASS SPECTROMETRY.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419; SER-420; SER-435;
RP SER-454; THR-460 AND THR-470, AND MASS SPECTROMETRY.
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-454; THR-460
RP AND THR-494, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
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.,
RA Buerckstuemmer T., 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 [15]
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.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
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
RT human 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.
CC -!- SUBUNIT: Monomer. Binds clathrin, ZBTB16/ZNF145 and ITSN1. Binds
CC ubiquitinated proteins (By similarity). Binds REPS2, EPS15, AP2A1
CC and AP2A2. Interacts with RALBP1 in a complex also containing NUMB
CC and TFAP2A during interphase and mitosis. Interacts with AP2B1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane;
CC Peripheral membrane protein (By similarity). Nucleus (By
CC similarity). Membrane, clathrin-coated pit (By similarity).
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. Detected in
CC presynaptic nerve terminals and in Golgi stacks. May shuttle to
CC the nucleus when associated with ZBTB16/ZNF145 (By similarity).
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 Note=Ref.1 (AAD38326) sequence differs from that shown due to a
CC frameshift in position 98;
CC Name=3;
CC IsoId=Q9Y6I3-3; Sequence=VSP_041011, VSP_041012;
CC Note=May be due to a competing donor splice site. No
CC experimental confirmation available;
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 with the AP-2 complex subunit AP2B1 (By similarity).
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.
CC -!- PTM: Ubiquitinated (By similarity).
CC -!- SIMILARITY: Belongs to the epsin family.
CC -!- SIMILARITY: Contains 1 ENTH (epsin N-terminal homology) domain.
CC -!- SIMILARITY: Contains 3 UIM (ubiquitin-interacting motif) repeats.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The bubble's bend -
CC Issue 42 of January 2004;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt042.shtml";
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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 RefSeq; NP_001123543.1; NM_001130071.1.
DR RefSeq; NP_001123544.1; NM_001130072.1.
DR RefSeq; NP_037465.2; NM_013333.3.
DR RefSeq; XP_005258886.1; XM_005258829.1.
DR RefSeq; XP_005258888.1; XM_005258831.1.
DR UniGene; Hs.279953; -.
DR PDB; 1INZ; NMR; -; A=1-144.
DR PDBsum; 1INZ; -.
DR ProteinModelPortal; Q9Y6I3; -.
DR SMR; Q9Y6I3; 1-158.
DR IntAct; Q9Y6I3; 9.
DR MINT; MINT-110599; -.
DR STRING; 9606.ENSP00000406209; -.
DR PhosphoSite; Q9Y6I3; -.
DR DMDM; 41017059; -.
DR PaxDb; Q9Y6I3; -.
DR PRIDE; Q9Y6I3; -.
DR DNASU; 29924; -.
DR Ensembl; ENST00000085079; ENSP00000085079; ENSG00000063245.
DR Ensembl; ENST00000270460; ENSP00000270460; ENSG00000063245.
DR Ensembl; ENST00000411543; ENSP00000406209; ENSG00000063245.
DR GeneID; 29924; -.
DR KEGG; hsa:29924; -.
DR UCSC; uc002qlw.3; human.
DR CTD; 29924; -.
DR GeneCards; GC19P056186; -.
DR H-InvDB; HIX0202721; -.
DR HGNC; HGNC:21604; EPN1.
DR HPA; CAB009729; -.
DR MIM; 607262; gene.
DR neXtProt; NX_Q9Y6I3; -.
DR PharmGKB; PA134860916; -.
DR eggNOG; NOG263730; -.
DR HOGENOM; HOG000008298; -.
DR HOVERGEN; HBG006690; -.
DR KO; K12471; -.
DR OMA; DPWGGTQ; -.
DR OrthoDB; EOG7F511Z; -.
DR PhylomeDB; Q9Y6I3; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SignaLink; Q9Y6I3; -.
DR EvolutionaryTrace; Q9Y6I3; -.
DR GeneWiki; EPN1; -.
DR GenomeRNAi; 29924; -.
DR NextBio; 52535; -.
DR PRO; PR:Q9Y6I3; -.
DR ArrayExpress; Q9Y6I3; -.
DR Bgee; Q9Y6I3; -.
DR CleanEx; HS_EPN1; -.
DR Genevestigator; Q9Y6I3; -.
DR GO; GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl.
DR GO; GO:0006897; P:endocytosis; TAS:ProtInc.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR Gene3D; 1.25.40.90; -; 1.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR013809; Epsin-like_N.
DR InterPro; IPR001026; Epsin_dom_N.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR Pfam; PF01417; ENTH; 1.
DR Pfam; PF02809; UIM; 2.
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;
KW Complete proteome; Cytoplasm; Endocytosis; Lipid-binding; Membrane;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1 576 Epsin-1.
FT /FTId=PRO_0000074513.
FT DOMAIN 12 144 ENTH.
FT REPEAT 183 202 UIM 1.
FT REPEAT 208 227 UIM 2.
FT REPEAT 233 252 UIM 3.
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 502 504 1.
FT REPEAT 518 520 2.
FT REPEAT 572 574 3.
FT REGION 274 379 8 X 3 AA repeats of [ED]-P-W.
FT REGION 502 574 3 X 3 AA repeats of N-P-F.
FT MOTIF 402 411 [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif.
FT COMPBIAS 267 573 Ala/Gly/Pro-rich.
FT BINDING 8 8 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 11 11 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 25 25 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 30 30 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 63 63 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 73 73 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT MOD_RES 382 382 Phosphoserine; by CDK1.
FT MOD_RES 419 419 Phosphoserine.
FT MOD_RES 420 420 Phosphoserine.
FT MOD_RES 435 435 Phosphoserine.
FT MOD_RES 454 454 Phosphoserine.
FT MOD_RES 460 460 Phosphothreonine.
FT MOD_RES 470 470 Phosphothreonine.
FT MOD_RES 494 494 Phosphothreonine.
FT VAR_SEQ 1 1 M -> MGDQSWLWNQAAPGVRSPVFACSVEKGNVPLVLSEH
FT LAHSRDPGSGAVRFLISPEPWASAILGTSGLLASPVLPAAL
FT DAVTCQHLPQPSSGSRPISPRIGALCPLLLQPGTM (in
FT isoform 2).
FT /FTId=VSP_041010.
FT VAR_SEQ 202 226 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_041011.
FT VAR_SEQ 393 393 Missing (in isoform 3).
FT /FTId=VSP_041012.
FT MUTAGEN 382 382 S->A: Abolishes phosphorylation by CDK1.
FT MUTAGEN 382 382 S->D: Abolishes phosphorylation by CDK1
FT and reduces REPS2 binding.
FT MUTAGEN 404 404 F->A: Reduces interaction with AP2B1.
FT HELIX 20 27
FT HELIX 39 47
FT HELIX 51 62
FT HELIX 63 65
FT HELIX 72 86
FT HELIX 90 98
FT HELIX 100 108
FT HELIX 121 134
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
//
ID EPN1_HUMAN Reviewed; 576 AA.
AC Q9Y6I3; Q86ST3; Q9HA18;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-MAY-2011, sequence version 2.
DT 22-JAN-2014, entry version 129.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA 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
RT project: 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
RP WITH 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.,
RA Kikuchi A.;
RT "Regulation of complex formation of POB1/epsin/adaptor protein complex
RT 2 by mitotic phosphorylation.";
RL J. Biol. Chem. 275:18399-18406(2000).
RN [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-494, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
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
RT endocytic cargo selection and clathrin coat assembly.";
RL Dev. Cell 10:329-342(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-454 AND THR-460, AND
RP MASS SPECTROMETRY.
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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [10]
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
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-454; THR-460
RP AND THR-494, AND MASS SPECTROMETRY.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419; SER-420; SER-435;
RP SER-454; THR-460 AND THR-470, AND MASS SPECTROMETRY.
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-454; THR-460
RP AND THR-494, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
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.,
RA Buerckstuemmer T., 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 [15]
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.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
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
RT human 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.
CC -!- SUBUNIT: Monomer. Binds clathrin, ZBTB16/ZNF145 and ITSN1. Binds
CC ubiquitinated proteins (By similarity). Binds REPS2, EPS15, AP2A1
CC and AP2A2. Interacts with RALBP1 in a complex also containing NUMB
CC and TFAP2A during interphase and mitosis. Interacts with AP2B1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane;
CC Peripheral membrane protein (By similarity). Nucleus (By
CC similarity). Membrane, clathrin-coated pit (By similarity).
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. Detected in
CC presynaptic nerve terminals and in Golgi stacks. May shuttle to
CC the nucleus when associated with ZBTB16/ZNF145 (By similarity).
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 Note=Ref.1 (AAD38326) sequence differs from that shown due to a
CC frameshift in position 98;
CC Name=3;
CC IsoId=Q9Y6I3-3; Sequence=VSP_041011, VSP_041012;
CC Note=May be due to a competing donor splice site. No
CC experimental confirmation available;
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 with the AP-2 complex subunit AP2B1 (By similarity).
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.
CC -!- PTM: Ubiquitinated (By similarity).
CC -!- SIMILARITY: Belongs to the epsin family.
CC -!- SIMILARITY: Contains 1 ENTH (epsin N-terminal homology) domain.
CC -!- SIMILARITY: Contains 3 UIM (ubiquitin-interacting motif) repeats.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The bubble's bend -
CC Issue 42 of January 2004;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt042.shtml";
CC -----------------------------------------------------------------------
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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 RefSeq; NP_001123543.1; NM_001130071.1.
DR RefSeq; NP_001123544.1; NM_001130072.1.
DR RefSeq; NP_037465.2; NM_013333.3.
DR RefSeq; XP_005258886.1; XM_005258829.1.
DR RefSeq; XP_005258888.1; XM_005258831.1.
DR UniGene; Hs.279953; -.
DR PDB; 1INZ; NMR; -; A=1-144.
DR PDBsum; 1INZ; -.
DR ProteinModelPortal; Q9Y6I3; -.
DR SMR; Q9Y6I3; 1-158.
DR IntAct; Q9Y6I3; 9.
DR MINT; MINT-110599; -.
DR STRING; 9606.ENSP00000406209; -.
DR PhosphoSite; Q9Y6I3; -.
DR DMDM; 41017059; -.
DR PaxDb; Q9Y6I3; -.
DR PRIDE; Q9Y6I3; -.
DR DNASU; 29924; -.
DR Ensembl; ENST00000085079; ENSP00000085079; ENSG00000063245.
DR Ensembl; ENST00000270460; ENSP00000270460; ENSG00000063245.
DR Ensembl; ENST00000411543; ENSP00000406209; ENSG00000063245.
DR GeneID; 29924; -.
DR KEGG; hsa:29924; -.
DR UCSC; uc002qlw.3; human.
DR CTD; 29924; -.
DR GeneCards; GC19P056186; -.
DR H-InvDB; HIX0202721; -.
DR HGNC; HGNC:21604; EPN1.
DR HPA; CAB009729; -.
DR MIM; 607262; gene.
DR neXtProt; NX_Q9Y6I3; -.
DR PharmGKB; PA134860916; -.
DR eggNOG; NOG263730; -.
DR HOGENOM; HOG000008298; -.
DR HOVERGEN; HBG006690; -.
DR KO; K12471; -.
DR OMA; DPWGGTQ; -.
DR OrthoDB; EOG7F511Z; -.
DR PhylomeDB; Q9Y6I3; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SignaLink; Q9Y6I3; -.
DR EvolutionaryTrace; Q9Y6I3; -.
DR GeneWiki; EPN1; -.
DR GenomeRNAi; 29924; -.
DR NextBio; 52535; -.
DR PRO; PR:Q9Y6I3; -.
DR ArrayExpress; Q9Y6I3; -.
DR Bgee; Q9Y6I3; -.
DR CleanEx; HS_EPN1; -.
DR Genevestigator; Q9Y6I3; -.
DR GO; GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl.
DR GO; GO:0006897; P:endocytosis; TAS:ProtInc.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR Gene3D; 1.25.40.90; -; 1.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR013809; Epsin-like_N.
DR InterPro; IPR001026; Epsin_dom_N.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR Pfam; PF01417; ENTH; 1.
DR Pfam; PF02809; UIM; 2.
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;
KW Complete proteome; Cytoplasm; Endocytosis; Lipid-binding; Membrane;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1 576 Epsin-1.
FT /FTId=PRO_0000074513.
FT DOMAIN 12 144 ENTH.
FT REPEAT 183 202 UIM 1.
FT REPEAT 208 227 UIM 2.
FT REPEAT 233 252 UIM 3.
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 502 504 1.
FT REPEAT 518 520 2.
FT REPEAT 572 574 3.
FT REGION 274 379 8 X 3 AA repeats of [ED]-P-W.
FT REGION 502 574 3 X 3 AA repeats of N-P-F.
FT MOTIF 402 411 [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif.
FT COMPBIAS 267 573 Ala/Gly/Pro-rich.
FT BINDING 8 8 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 11 11 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 25 25 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 30 30 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 63 63 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 73 73 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT MOD_RES 382 382 Phosphoserine; by CDK1.
FT MOD_RES 419 419 Phosphoserine.
FT MOD_RES 420 420 Phosphoserine.
FT MOD_RES 435 435 Phosphoserine.
FT MOD_RES 454 454 Phosphoserine.
FT MOD_RES 460 460 Phosphothreonine.
FT MOD_RES 470 470 Phosphothreonine.
FT MOD_RES 494 494 Phosphothreonine.
FT VAR_SEQ 1 1 M -> MGDQSWLWNQAAPGVRSPVFACSVEKGNVPLVLSEH
FT LAHSRDPGSGAVRFLISPEPWASAILGTSGLLASPVLPAAL
FT DAVTCQHLPQPSSGSRPISPRIGALCPLLLQPGTM (in
FT isoform 2).
FT /FTId=VSP_041010.
FT VAR_SEQ 202 226 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_041011.
FT VAR_SEQ 393 393 Missing (in isoform 3).
FT /FTId=VSP_041012.
FT MUTAGEN 382 382 S->A: Abolishes phosphorylation by CDK1.
FT MUTAGEN 382 382 S->D: Abolishes phosphorylation by CDK1
FT and reduces REPS2 binding.
FT MUTAGEN 404 404 F->A: Reduces interaction with AP2B1.
FT HELIX 20 27
FT HELIX 39 47
FT HELIX 51 62
FT HELIX 63 65
FT HELIX 72 86
FT HELIX 90 98
FT HELIX 100 108
FT HELIX 121 134
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
//
MIM
607262
*RECORD*
*FIELD* NO
607262
*FIELD* TI
*607262 EPSIN 1; EPN1
;;EPSIN
*FIELD* TX
DESCRIPTION
EPN1 is an endocytic accessory protein that interacts with EPS15
read more(600051), the alpha subunit of the clathrin adaptor AP2 (AP2A1; 601026),
and clathrin (see 118960), as well as with other accessory proteins for
the endocytosis of clathrin-coated vesicles.
CLONING
Chen et al. (1998) cloned rat Epn1 from a rat brain cDNA library. The
deduced 576-amino acid protein contains several conserved asp-pro-trp
(DPW) repeats in its central region, a Cdc2 (116940) phosphorylation
site, and 3 arg-pro-phe (NPF) repeats in its C-terminal region. Northern
blot analysis detected a 2.6-kb transcript in all rat tissues tested,
and Western blot analysis confirmed ubiquitous expression.
Immunofluorescence localization using rat brain frozen sections revealed
colocalization of Epn1 with Eps15, synaptophysin (313475), and clathrin
in nerve terminals.
Morinaka et al. (1999) identified EPN1 as an 84-kD protein that binds
bovine brain Pob1 (REPS2; 300317). By searching an EST database, PCR,
and 5-prime and 3-prime RACE of a brain cDNA library, they cloned human
EPN1. The deduced 551-amino acid protein contains an epsin N-terminal
homology (ENTH) region, which includes 1 DPW sequence, followed by 8
central DPW repeats, a single LVDLD sequence, and 3 NPF repeats at the C
terminus. The LVDLD sequence is a clathrin-binding motif, and NPF is the
core motif of an EPS15 homology (EH) domain-binding domain.
GENE FUNCTION
Using truncation mutants of rat brain Epn1, Chen et al. (1998)
determined that the central region of Epn1, which contains the DPW
repeats, binds AP2, and the C-terminal region binds Eps15. Rat Epn1
associated with clathrin coats in situ and could be coprecipitated with
AP2 and Eps15. It did not copurify with mature clathrin-coated vesicles.
Chen et al. (1998) concluded that EPN1 may participate with EPS15 in the
molecular rearrangement of the clathrin coats that are required for
coated-pit invagination and vesicle fission.
Using in vitro pull-down assays, Morinaka et al. (1999) determined that
the EH domain of REPS2 interacts specifically with a 10-amino acid
C-terminal peptide of EPN1 containing the NPF sequence. Expression of
EPN1 in CHO cells overexpressing insulin receptor (INSR; 147670)
inhibited internalization of insulin, but it did not affect
insulin-binding or autophosphorylation of INSR.
Kariya et al. (2000) found that EPN1, RALA-binding protein-1 (RALBP1;
605801), REPS2, and EPS15 formed a complex with AP2A1 in CHO cells. They
noted that EPN1 contains a single putative phosphorylation site at
ser357, and they transfected human EPN1 containing a point mutation
(ser357 to asp) at this site into CHO cells overexpressing INSR.
Phosphorylated EPN1 and the ser357-to-asp mutant formed a complex with
AP2A1 less efficiently than nonphosphorylated wildtype EPN1.
Phosphorylation of EPN1 also inhibited binding with the EH domain of
REPS2, suggesting that phosphorylation of EPN1 inhibits
receptor-mediated endocytosis by disassembly of its complex with REPS2
and AP2A1.
Ford et al. (2002) found that EPN1 expressed in transfected COS cells
showed a general cytoplasmic distribution or accumulation in puncta on
the plasma membrane. EPN1 colocalized with AP2, clathrin, EPS15, and
dynamin (see 602377). The presence of dynamin suggested that the puncta
represent endocytically incompetent coated pits. Ford et al. (2002)
determined that the ENTH domain of EPN1 binds the membrane lipid
phosphatidylinositol-4,5-bisphosphate, or PtdIns(4,5)P2. Monomeric EPN1
modified membrane curvature upon binding to PtdIns(4,5)P2. On lipid
monolayers, EPN1 alone was sufficient to facilitate the formation of
clathrin-coated invaginations.
Using fluorescence microscopy, Chen and Zhuang (2008) identified EPN1 as
a cargo-specific adaptor for influenza virus entry through the
clathrin-mediated pathway. EPN1 was recruited to virus-binding sites in
synchrony with the assembly of clathrin-coated pits. Knockdown of EPN1
by small interfering RNA inhibited clathrin-mediated endocytosis and
caused the virus to enter through a clathrin-independent pathway. EPN1
was not required for clathrin-mediated endocytosis of transferrin (TF;
190000), EGF, and low density lipoprotein.
BIOCHEMICAL FEATURES
Endocytic proteins such as epsin, AP180 (603025), and HIP1R (605613)
share a conserved modular region termed the ENTH domain, which plays a
crucial role in clathrin-mediated endocytosis. Itoh et al. (2001)
demonstrated a strong affinity of the ENTH domain for PtdIns(4,5)P2.
With nuclear magnetic resonance analysis of the epsin ENTH domain, they
determined that a cleft formed with positively charged residues
contributed to phosphoinositide binding. Overexpression of a mutant,
epsin lys76 to ala, with an ENTH domain defective in phosphoinositide
binding blocked epidermal growth factor internalization in COS-7 cells.
Thus, interaction between the ENTH domain and PtdIns(4,5)P2 is essential
for endocytosis mediated by clathrin-coated pits.
*FIELD* RF
1. Chen, C.; Zhuang, X.: Epsin 1 is a cargo-specific adaptor for
the clathrin-mediated endocytosis of the influenza virus. Proc. Nat.
Acad. Sci. 105: 11790-11795, 2008.
2. Chen, H.; Fre, S.; Slepnev, V. I.; Capua, M. R.; Takei, K.; Butler,
M. H.; Di Fiore, P. P.; De Camilli, P.: Epsin is an EH-domain-binding
protein implicated in clathrin-mediated endocytosis. Nature 394:
793-797, 1998.
3. Ford, M. G. J.; Mills, I. G.; Peter, B. J.; Vallis, Y.; Praefcke,
G. J. K.; Evans, P. R.; McMahon, H. T.: Curvature of clathrin-coated
pits driven by epsin. Nature 419: 361-366, 2002.
4. Itoh, T.; Koshiba, S.; Kigawa, T.; Kikuchi, A.; Yokoyama, S.; Takenawa,
T.: Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate
binding and endocytosis. Science 291: 1047-1051, 2001.
5. Kariya, K.; Koyama, S.; Nakashima, S.; Oshiro, T.; Morinaka, K.;
Kikuchi, A.: Regulation of complex formation of POB1/epsin/adaptor
protein complex 2 by mitotic phosphorylation. J. Biol. Chem. 275:
18399-18406, 2000.
6. Morinaka, K.; Koyama, S.; Nakashima, S.; Hinoi, T.; Okawa, K.;
Iwamatsu, A.; Kikuchi, A.: Epsin binds to the EH domain of POB1 and
regulates receptor-mediated endocytosis. Oncogene 18: 5915-5922,
1999.
*FIELD* CN
Paul J. Converse - updated: 4/21/2009
*FIELD* CD
Patricia A. Hartz: 9/27/2002
*FIELD* ED
alopez: 05/14/2009
mgross: 4/22/2009
terry: 4/21/2009
joanna: 12/7/2004
terry: 1/2/2003
mgross: 9/27/2002
*RECORD*
*FIELD* NO
607262
*FIELD* TI
*607262 EPSIN 1; EPN1
;;EPSIN
*FIELD* TX
DESCRIPTION
EPN1 is an endocytic accessory protein that interacts with EPS15
read more(600051), the alpha subunit of the clathrin adaptor AP2 (AP2A1; 601026),
and clathrin (see 118960), as well as with other accessory proteins for
the endocytosis of clathrin-coated vesicles.
CLONING
Chen et al. (1998) cloned rat Epn1 from a rat brain cDNA library. The
deduced 576-amino acid protein contains several conserved asp-pro-trp
(DPW) repeats in its central region, a Cdc2 (116940) phosphorylation
site, and 3 arg-pro-phe (NPF) repeats in its C-terminal region. Northern
blot analysis detected a 2.6-kb transcript in all rat tissues tested,
and Western blot analysis confirmed ubiquitous expression.
Immunofluorescence localization using rat brain frozen sections revealed
colocalization of Epn1 with Eps15, synaptophysin (313475), and clathrin
in nerve terminals.
Morinaka et al. (1999) identified EPN1 as an 84-kD protein that binds
bovine brain Pob1 (REPS2; 300317). By searching an EST database, PCR,
and 5-prime and 3-prime RACE of a brain cDNA library, they cloned human
EPN1. The deduced 551-amino acid protein contains an epsin N-terminal
homology (ENTH) region, which includes 1 DPW sequence, followed by 8
central DPW repeats, a single LVDLD sequence, and 3 NPF repeats at the C
terminus. The LVDLD sequence is a clathrin-binding motif, and NPF is the
core motif of an EPS15 homology (EH) domain-binding domain.
GENE FUNCTION
Using truncation mutants of rat brain Epn1, Chen et al. (1998)
determined that the central region of Epn1, which contains the DPW
repeats, binds AP2, and the C-terminal region binds Eps15. Rat Epn1
associated with clathrin coats in situ and could be coprecipitated with
AP2 and Eps15. It did not copurify with mature clathrin-coated vesicles.
Chen et al. (1998) concluded that EPN1 may participate with EPS15 in the
molecular rearrangement of the clathrin coats that are required for
coated-pit invagination and vesicle fission.
Using in vitro pull-down assays, Morinaka et al. (1999) determined that
the EH domain of REPS2 interacts specifically with a 10-amino acid
C-terminal peptide of EPN1 containing the NPF sequence. Expression of
EPN1 in CHO cells overexpressing insulin receptor (INSR; 147670)
inhibited internalization of insulin, but it did not affect
insulin-binding or autophosphorylation of INSR.
Kariya et al. (2000) found that EPN1, RALA-binding protein-1 (RALBP1;
605801), REPS2, and EPS15 formed a complex with AP2A1 in CHO cells. They
noted that EPN1 contains a single putative phosphorylation site at
ser357, and they transfected human EPN1 containing a point mutation
(ser357 to asp) at this site into CHO cells overexpressing INSR.
Phosphorylated EPN1 and the ser357-to-asp mutant formed a complex with
AP2A1 less efficiently than nonphosphorylated wildtype EPN1.
Phosphorylation of EPN1 also inhibited binding with the EH domain of
REPS2, suggesting that phosphorylation of EPN1 inhibits
receptor-mediated endocytosis by disassembly of its complex with REPS2
and AP2A1.
Ford et al. (2002) found that EPN1 expressed in transfected COS cells
showed a general cytoplasmic distribution or accumulation in puncta on
the plasma membrane. EPN1 colocalized with AP2, clathrin, EPS15, and
dynamin (see 602377). The presence of dynamin suggested that the puncta
represent endocytically incompetent coated pits. Ford et al. (2002)
determined that the ENTH domain of EPN1 binds the membrane lipid
phosphatidylinositol-4,5-bisphosphate, or PtdIns(4,5)P2. Monomeric EPN1
modified membrane curvature upon binding to PtdIns(4,5)P2. On lipid
monolayers, EPN1 alone was sufficient to facilitate the formation of
clathrin-coated invaginations.
Using fluorescence microscopy, Chen and Zhuang (2008) identified EPN1 as
a cargo-specific adaptor for influenza virus entry through the
clathrin-mediated pathway. EPN1 was recruited to virus-binding sites in
synchrony with the assembly of clathrin-coated pits. Knockdown of EPN1
by small interfering RNA inhibited clathrin-mediated endocytosis and
caused the virus to enter through a clathrin-independent pathway. EPN1
was not required for clathrin-mediated endocytosis of transferrin (TF;
190000), EGF, and low density lipoprotein.
BIOCHEMICAL FEATURES
Endocytic proteins such as epsin, AP180 (603025), and HIP1R (605613)
share a conserved modular region termed the ENTH domain, which plays a
crucial role in clathrin-mediated endocytosis. Itoh et al. (2001)
demonstrated a strong affinity of the ENTH domain for PtdIns(4,5)P2.
With nuclear magnetic resonance analysis of the epsin ENTH domain, they
determined that a cleft formed with positively charged residues
contributed to phosphoinositide binding. Overexpression of a mutant,
epsin lys76 to ala, with an ENTH domain defective in phosphoinositide
binding blocked epidermal growth factor internalization in COS-7 cells.
Thus, interaction between the ENTH domain and PtdIns(4,5)P2 is essential
for endocytosis mediated by clathrin-coated pits.
*FIELD* RF
1. Chen, C.; Zhuang, X.: Epsin 1 is a cargo-specific adaptor for
the clathrin-mediated endocytosis of the influenza virus. Proc. Nat.
Acad. Sci. 105: 11790-11795, 2008.
2. Chen, H.; Fre, S.; Slepnev, V. I.; Capua, M. R.; Takei, K.; Butler,
M. H.; Di Fiore, P. P.; De Camilli, P.: Epsin is an EH-domain-binding
protein implicated in clathrin-mediated endocytosis. Nature 394:
793-797, 1998.
3. Ford, M. G. J.; Mills, I. G.; Peter, B. J.; Vallis, Y.; Praefcke,
G. J. K.; Evans, P. R.; McMahon, H. T.: Curvature of clathrin-coated
pits driven by epsin. Nature 419: 361-366, 2002.
4. Itoh, T.; Koshiba, S.; Kigawa, T.; Kikuchi, A.; Yokoyama, S.; Takenawa,
T.: Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate
binding and endocytosis. Science 291: 1047-1051, 2001.
5. Kariya, K.; Koyama, S.; Nakashima, S.; Oshiro, T.; Morinaka, K.;
Kikuchi, A.: Regulation of complex formation of POB1/epsin/adaptor
protein complex 2 by mitotic phosphorylation. J. Biol. Chem. 275:
18399-18406, 2000.
6. Morinaka, K.; Koyama, S.; Nakashima, S.; Hinoi, T.; Okawa, K.;
Iwamatsu, A.; Kikuchi, A.: Epsin binds to the EH domain of POB1 and
regulates receptor-mediated endocytosis. Oncogene 18: 5915-5922,
1999.
*FIELD* CN
Paul J. Converse - updated: 4/21/2009
*FIELD* CD
Patricia A. Hartz: 9/27/2002
*FIELD* ED
alopez: 05/14/2009
mgross: 4/22/2009
terry: 4/21/2009
joanna: 12/7/2004
terry: 1/2/2003
mgross: 9/27/2002