EPN1_MOUSE
ID EPN1_MOUSE Reviewed; 575 AA.
AC Q80VP1; O70446; Q6NX78;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 3.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Epsin-1;
DE AltName: Full=EPS-15-interacting protein 1;
DE AltName: Full=Intersectin-EH-binding protein 1;
DE Short=Ibp1;
GN Name=Epn1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Colon, Limb, and Olfactory epithelium;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 365-575 (ISOFORM 2), AND INTERACTION WITH
RP ITSN1.
RC TISSUE=Embryo;
RX PubMed=9813051; DOI=10.1074/jbc.273.47.31401;
RA Yamabhai M., Hoffman N.G., Hardison N.L., McPherson P.S., Castagnoli L.,
RA Cesareni G., Kay B.K.;
RT "Intersectin, a novel adaptor protein with two eps15 homology and five src
RT homology 3 domains.";
RL J. Biol. Chem. 273:31401-31407(1998).
RN [3]
RP PHOSPHORYLATION, AND INTERACTION WITH AP2A1 AND AP2A2.
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-dependent
RT dephosphorylation in nerve terminals.";
RL J. Biol. Chem. 274:3257-3260(1999).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-469, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-418; SER-419; THR-420;
RP THR-459; THR-469; SER-472 AND THR-493, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-533, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
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 (By similarity).
CC {ECO:0000250|UniProtKB:O88339, ECO:0000250|UniProtKB:Q9Y6I3}.
CC -!- SUBUNIT: Monomer. Binds clathrin and ZBTB16/ZNF145 (By similarity).
CC Binds ubiquitinated proteins (By similarity). Interacts with RALBP1 in
CC a complex also containing NUMB and TFAP2A during interphase and mitosis
CC (By similarity). Interacts with AP2B1 (By similarity). Interacts with
CC UBQLN2 (By similarity). Interacts with ITSN1. Interacts with AP2A1 and
CC AP2A2. Interacts with REPS2; the interaction is direct (By similarity).
CC Interacts with EPS15; the interaction is direct (By similarity).
CC {ECO:0000250|UniProtKB:O88339, ECO:0000250|UniProtKB:Q9Y6I3,
CC ECO:0000269|PubMed:9813051, ECO:0000269|PubMed:9920862}.
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=2;
CC Name=1;
CC IsoId=Q80VP1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80VP1-2; Sequence=VSP_009153;
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 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:9920862}.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the epsin family. {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";
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DR EMBL; BC046962; AAH46962.2; -; mRNA.
DR EMBL; BC067206; AAH67206.1; -; mRNA.
DR EMBL; BC099682; AAH99682.1; -; mRNA.
DR EMBL; AF057285; AAC97475.1; -; mRNA.
DR CCDS; CCDS20758.1; -. [Q80VP1-1]
DR CCDS; CCDS90155.1; -. [Q80VP1-2]
DR RefSeq; NP_001239383.1; NM_001252454.1. [Q80VP1-1]
DR RefSeq; NP_034277.1; NM_010147.4. [Q80VP1-1]
DR RefSeq; XP_006539592.2; XM_006539529.3. [Q80VP1-2]
DR RefSeq; XP_006539594.2; XM_006539531.3. [Q80VP1-2]
DR RefSeq; XP_006539596.1; XM_006539533.1.
DR RefSeq; XP_006539597.1; XM_006539534.1. [Q80VP1-2]
DR RefSeq; XP_006539598.1; XM_006539535.1. [Q80VP1-2]
DR RefSeq; XP_006539599.1; XM_006539536.1. [Q80VP1-2]
DR AlphaFoldDB; Q80VP1; -.
DR BMRB; Q80VP1; -.
DR SMR; Q80VP1; -.
DR BioGRID; 199485; 14.
DR DIP; DIP-43943N; -.
DR ELM; Q80VP1; -.
DR IntAct; Q80VP1; 5.
DR MINT; Q80VP1; -.
DR STRING; 10090.ENSMUSP00000096445; -.
DR iPTMnet; Q80VP1; -.
DR PhosphoSitePlus; Q80VP1; -.
DR EPD; Q80VP1; -.
DR jPOST; Q80VP1; -.
DR MaxQB; Q80VP1; -.
DR PaxDb; Q80VP1; -.
DR PeptideAtlas; Q80VP1; -.
DR PRIDE; Q80VP1; -.
DR ProteomicsDB; 275668; -. [Q80VP1-1]
DR ProteomicsDB; 275669; -. [Q80VP1-2]
DR Antibodypedia; 4051; 221 antibodies from 30 providers.
DR DNASU; 13854; -.
DR Ensembl; ENSMUST00000045277; ENSMUSP00000043340; ENSMUSG00000035203. [Q80VP1-1]
DR Ensembl; ENSMUST00000098845; ENSMUSP00000096445; ENSMUSG00000035203. [Q80VP1-1]
DR Ensembl; ENSMUST00000208634; ENSMUSP00000146638; ENSMUSG00000035203. [Q80VP1-2]
DR GeneID; 13854; -.
DR KEGG; mmu:13854; -.
DR UCSC; uc009ezx.2; mouse. [Q80VP1-1]
DR CTD; 29924; -.
DR MGI; MGI:1333763; Epn1.
DR VEuPathDB; HostDB:ENSMUSG00000035203; -.
DR eggNOG; KOG2056; Eukaryota.
DR GeneTree; ENSGT00940000160411; -.
DR HOGENOM; CLU_012678_4_2_1; -.
DR InParanoid; Q80VP1; -.
DR OMA; CEKADEM; -.
DR OrthoDB; 1263849at2759; -.
DR PhylomeDB; Q80VP1; -.
DR TreeFam; TF313361; -.
DR Reactome; R-MMU-182971; EGFR downregulation.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 13854; 8 hits in 73 CRISPR screens.
DR ChiTaRS; Epn1; mouse.
DR PRO; PR:Q80VP1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q80VP1; protein.
DR Bgee; ENSMUSG00000035203; Expressed in ileal epithelium and 232 other tissues.
DR ExpressionAtlas; Q80VP1; baseline and differential.
DR Genevisible; Q80VP1; MM.
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; ISO:MGI.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISO:MGI.
DR GO; GO:0098890; C:extrinsic component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0098888; C:extrinsic component of presynaptic membrane; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098794; C:postsynapse; ISO:MGI.
DR GO; GO:0098793; C:presynapse; ISO:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:MGI.
DR GO; GO:0035615; F:clathrin adaptor activity; ISO:MGI.
DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
DR GO; GO:0005543; F:phospholipid binding; IBA:GO_Central.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0048568; P:embryonic organ development; IGI:MGI.
DR GO; GO:0006897; P:endocytosis; ISO:MGI.
DR GO; GO:0007565; P:female pregnancy; IGI:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR GO; GO:0090148; P:membrane fission; ISO:MGI.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; ISO:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IGI:MGI.
DR GO; GO:1905445; P:positive regulation of clathrin coat assembly; ISO:MGI.
DR DisProt; DP01993; -.
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 Alternative splicing; Cell membrane; Coated pit; Cytoplasm; Endocytosis;
KW Lipid-binding; Membrane; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..575
FT /note="Epsin-1"
FT /id="PRO_0000074514"
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 501..503
FT /note="1"
FT REPEAT 517..519
FT /note="2"
FT REPEAT 571..573
FT /note="3"
FT REGION 150..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 274..379
FT /note="8 X 3 AA repeats of D-P-W"
FT REGION 501..573
FT /note="3 X 3 AA repeats of N-P-F"
FT MOTIF 401..410
FT /note="[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif"
FT COMPBIAS 455..469
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 506..520
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 537..575
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6I3"
FT MOD_RES 418
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 420
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6I3"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6I3"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6I3"
FT MOD_RES 459
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 463
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6I3"
FT MOD_RES 469
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 472
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 493
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 533
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 392
FT /note="A -> AA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9813051"
FT /id="VSP_009153"
SQ SEQUENCE 575 AA; 60212 MW; 70B8011EB3AE5C4C 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 AASDPWGGPA
VPPAADPWGG AAPTPASGDP WRPAAPTGPS VDPWGGTPAP AAGEGPTPDP WGSSDGGAPV
SGPPSSDPWA PAPAFSDPWG GSPAKPSSNG TAVGGFDTEP DEFSDFDRLR TALPTSGSST
GELELLAGEV PARSPGAFDM SGVGGSLAES VGSPPPAATP TPTPPTRKTP ESFLGPNAAL
VDLDSLVSRP GPTPPGSKAS NPFLPSGAPP TGPSVTNPFQ PAPPATLTLN QLRLSPVPPV
PGAPPTYISP LGGGPGLPPM MPPGPPAPNT NPFLL
