CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007565
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Epidermal growth factor receptor substrate 15 
Protein Synonyms/Alias
 Protein Eps15; Protein AF-1p 
Gene Name
 EPS15 
Gene Synonyms/Alias
 AF1P 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
413AQLEEQLKEVRKKCAubiquitination[1, 2]
495EISSMQMKLMEMKDLubiquitination[1, 2]
638FKDDPFGKIDPFGGDubiquitination[1, 2]
648PFGGDPFKGSDPFASubiquitination[3, 4]
754VSNVVITKNVFEETSubiquitination[1, 2, 4, 5, 6]
763VFEETSVKSEDEPPAubiquitination[5]
788PCPLPPGKRSINKLDubiquitination[1, 2, 4, 6, 7]
793PGKRSINKLDSPDPFubiquitination[1, 2, 4, 5, 6]
801LDSPDPFKLNDPFQPubiquitination[1, 2, 4, 5, 7]
816FPGNDSPKEKDPEIFubiquitination[1, 2, 5]
818GNDSPKEKDPEIFCDubiquitination[1, 2, 4, 5]
860EDMIEWAKRESEREEubiquitination[5]
890ELAIALSKSEISEA*ubiquitination[5]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [7] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
Functional Description
 Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta- 1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. 
Sequence Annotation
 DOMAIN 15 104 EH 1.
 DOMAIN 128 216 EH 2.
 DOMAIN 160 195 EF-hand 1.
 DOMAIN 223 258 EF-hand 2.
 DOMAIN 224 314 EH 3.
 REPEAT 599 601 1.
 REPEAT 623 625 2.
 REPEAT 629 631 3.
 REPEAT 634 636 4.
 REPEAT 640 642 5.
 REPEAT 645 647 6.
 REPEAT 651 653 7.
 REPEAT 664 666 8.
 REPEAT 672 674 9.
 REPEAT 692 694 10.
 REPEAT 709 711 11.
 REPEAT 737 739 12.
 REPEAT 798 800 13.
 REPEAT 804 806 14.
 REPEAT 825 827 15.
 REPEAT 851 870 UIM 1.
 REPEAT 877 896 UIM 2.
 REGION 2 330 Interaction with DAB2 (By similarity).
 REGION 599 827 15 X 3 AA repeats of D-P-F.
 MOTIF 768 774 SH3-binding.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 108 108 Phosphoserine.
 MOD_RES 140 140 Phosphoserine.
 MOD_RES 323 323 Phosphoserine.
 MOD_RES 324 324 Phosphoserine.
 MOD_RES 467 467 Phosphoserine.
 MOD_RES 470 470 Phosphoserine.
 MOD_RES 485 485 Phosphoserine.
 MOD_RES 562 562 Phosphoserine (By similarity).
 MOD_RES 563 563 Phosphoserine (By similarity).
 MOD_RES 777 777 Phosphothreonine (By similarity).
 MOD_RES 779 779 Phosphothreonine (By similarity).
 MOD_RES 790 790 Phosphoserine.
 MOD_RES 796 796 Phosphoserine.
 MOD_RES 814 814 Phosphoserine.
 MOD_RES 849 849 Phosphotyrosine; by EGFR.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Calcium; Cell membrane; Chromosomal rearrangement; Coated pit; Complete proteome; Cytoplasm; Endocytosis; Endosome; Membrane; Metal-binding; Phosphoprotein; Polymorphism; Protein transport; Proto-oncogene; Reference proteome; Repeat; SH3-binding; Transport. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 896 AA 
Protein Sequence
MAAAAQLSLT QLSSGNPVYE KYYRQVDTGN TGRVLASDAA AFLKKSGLPD LILGKIWDLA 60
DTDGKGILNK QEFFVALRLV ACAQNGLEVS LSSLNLAVPP PRFHDTSSPL LISGTSAAEL 120
PWAVKPEDKA KYDAIFDSLS PVNGFLSGDK VKPVLLNSKL PVDILGRVWE LSDIDHDGML 180
DRDEFAVAMF LVYCALEKEP VPMSLPPALV PPSKRKTWVV SPAEKAKYDE IFLKTDKDMD 240
GFVSGLEVRE IFLKTGLPST LLAHIWSLCD TKDCGKLSKD QFALAFHLIS QKLIKGIDPP 300
HVLTPEMIPP SDRASLQKNI IGSSPVADFS AIKELDTLNN EIVDLQREKN NVEQDLKEKE 360
DTIKQRTSEV QDLQDEVQRE NTNLQKLQAQ KQQVQELLDE LDEQKAQLEE QLKEVRKKCA 420
EEAQLISSLK AELTSQESQI STYEEELAKA REELSRLQQE TAELEESVES GKAQLEPLQQ 480
HLQDSQQEIS SMQMKLMEMK DLENHNSQLN WCSSPHSILV NGATDYCSLS TSSSETANLN 540
EHVEGQSNLE SEPIHQESPA RSSPELLPSG VTDENEVTTA VTEKVCSELD NNRHSKEEDP 600
FNVDSSSLTG PVADTNLDFF QSDPFVGSDP FKDDPFGKID PFGGDPFKGS DPFASDCFFR 660
QSTDPFATSS TDPFSAANNS SITSVETLKH NDPFAPGGTV VAASDSATDP FASVFGNESF 720
GGGFADFSTL SKVNNEDPFR SATSSSVSNV VITKNVFEET SVKSEDEPPA LPPKIGTPTR 780
PCPLPPGKRS INKLDSPDPF KLNDPFQPFP GNDSPKEKDP EIFCDPFTSA TTTTNKEADP 840
SNFANFSAYP SEEDMIEWAK RESEREEEQR LARLNQQEQE DLELAIALSK SEISEA 896 
Gene Ontology
 GO:0030122; C:AP-2 adaptor complex; IEA:Compara.
 GO:0060170; C:cilium membrane; IEA:Compara.
 GO:0005905; C:coated pit; TAS:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
 GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
 GO:0005886; C:plasma membrane; IDA:HGNC.
 GO:0005509; F:calcium ion binding; IEA:InterPro.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0048268; P:clathrin coat assembly; IDA:BHF-UCL.
 GO:0032456; P:endocytic recycling; IC:BHF-UCL.
 GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0015031; P:protein transport; IEA:UniProtKB-KW. 
Interpro
 IPR011992; EF-hand-like_dom.
 IPR018247; EF_Hand_1_Ca_BS.
 IPR002048; EF_hand_dom.
 IPR000261; EPS15_homology.
 IPR003903; Ubiquitin-int_motif. 
Pfam
  
SMART
 SM00054; EFh
 SM00027; EH
 SM00726; UIM 
PROSITE
 PS00018; EF_HAND_1
 PS50222; EF_HAND_2
 PS50031; EH
 PS50330; UIM 
PRINTS