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Reviewed, UniProtKB/Swiss-Prot P42566 (EP15_HUMAN)

Last modified November 25, 2008. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Epidermal growth factor receptor substrate 15
      Short name=Protein Eps15
Alternative name(s):
    AF-1p protein
Gene names
Name: EPS15
Synonyms: AF1P
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length896 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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 By similarity. Plays a role in the assembly of clathrin-coated pits.

Subunit structure

Heterotrimer; composed of EPS15, HGS, and either STAM1 or STAM2. Binds AP2A2 and AP2B1. Binds STON2 and EPN1. Interacts with CRK via its SH3-binding sites. Interacts with SH3BP4/TTP.

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note= Recruited to the plasma membrane upon EGFR activation and localizes to coated pits.

Tissue specificity

Ubiquitously expressed.

Domain

The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.

Post-translational modification

Phosphorylation on Tyr-849 is involved in the internalization of EGFR. Not required for membrane translocation after EGF treatment or for targeting to coated pits, but essential for a subsequent step in EGFR endocytosis By similarity. Phosphorylated on serine upon DNA damage, probably by ATM or ATR.

Involvement in disease

A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein.

Sequence similarities

Contains 2 EF-hand domains.

Contains 3 EH domains.

Contains 2 UIM (ubiquitin-interacting motif) repeats.

Ontologies

Keywords

   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   DiseaseProto-oncogene
   DomainRepeat
SH3-binding
   LigandCalcium
   PTMPhosphoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Biological processcell proliferation Ref.1

Traceable author statement. Source: ProtInc

epidermal growth factor receptor signaling pathway Ref.1

Traceable author statement. Source: ProtInc

vesicle organization

Traceable author statement. Source: UniProtKB

   Cellular componentcoated pit

Traceable author statement. Source: UniProtKB

cytosol

Inferred from Experiment. Source: Reactome

   Molecular functionSH3 domain binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 896896Epidermal growth factor receptor substrate 15
PRO_0000146116

Regions

Domain15 – 10490EH 1
Domain128 – 21689EH 2
Domain160 – 19536EF-hand 1
Domain223 – 25836EF-hand 2
Domain224 – 31491EH 3
Repeat599 – 60131
Repeat623 – 62532
Repeat629 – 63133
Repeat634 – 63634
Repeat640 – 64235
Repeat645 – 64736
Repeat651 – 65337
Repeat664 – 66638
Repeat672 – 67439
Repeat692 – 694310
Repeat709 – 711311
Repeat737 – 739312
Repeat798 – 800313
Repeat804 – 806314
Repeat825 – 827315
Repeat851 – 87020UIM 1
Repeat877 – 89620UIM 2
Calcium binding173 – 184121
Calcium binding236 – 247122
Region599 – 82722915 X 3 AA repeats of D-P-F
Motif768 – 7747SH3-binding
Compositional bias768 – 85083Pro-rich

Amino acid modifications

Modified residue1401Phosphoserine
Modified residue3231Phosphoserine
Modified residue3241Phosphoserine
Modified residue4851Phosphoserine
Modified residue5621Phosphoserine By similarity
Modified residue5631Phosphoserine By similarity
Modified residue7771Phosphothreonine
Modified residue7791Phosphothreonine By similarity
Modified residue7961Phosphoserine
Modified residue8141Phosphoserine
Modified residue8491Phosphotyrosine; by EGFR By similarity

Natural variations

Natural variant8221I → M: dbSNP rs17567.
VAR_016142

Experimental info

Mutagenesis1541V → E: Loss of interaction with STON2 NPF motifs
Mutagenesis1691W → A: Loss of interaction with STON2 NPF motifs

Secondary structure

................................. 896
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42566-1 [UniParc].

Last modified June 7, 2005. Version 2.
Checksum: A1B9FE15B47ABAFF

FASTA89698,656
        10         20         30         40         50         60 
MAAAAQLSLT QLSSGNPVYE KYYRQVDTGN TGRVLASDAA AFLKKSGLPD LILGKIWDLA 

        70         80         90        100        110        120 
DTDGKGILNK QEFFVALRLV ACAQNGLEVS LSSLNLAVPP PRFHDTSSPL LISGTSAAEL 

       130        140        150        160        170        180 
PWAVKPEDKA KYDAIFDSLS PVNGFLSGDK VKPVLLNSKL PVDILGRVWE LSDIDHDGML 

       190        200        210        220        230        240 
DRDEFAVAMF LVYCALEKEP VPMSLPPALV PPSKRKTWVV SPAEKAKYDE IFLKTDKDMD 

       250        260        270        280        290        300 
GFVSGLEVRE IFLKTGLPST LLAHIWSLCD TKDCGKLSKD QFALAFHLIS QKLIKGIDPP 

       310        320        330        340        350        360 
HVLTPEMIPP SDRASLQKNI IGSSPVADFS AIKELDTLNN EIVDLQREKN NVEQDLKEKE 

       370        380        390        400        410        420 
DTIKQRTSEV QDLQDEVQRE NTNLQKLQAQ KQQVQELLDE LDEQKAQLEE QLKEVRKKCA 

       430        440        450        460        470        480 
EEAQLISSLK AELTSQESQI STYEEELAKA REELSRLQQE TAELEESVES GKAQLEPLQQ 

       490        500        510        520        530        540 
HLQDSQQEIS SMQMKLMEMK DLENHNSQLN WCSSPHSILV NGATDYCSLS TSSSETANLN 

       550        560        570        580        590        600 
EHVEGQSNLE SEPIHQESPA RSSPELLPSG VTDENEVTTA VTEKVCSELD NNRHSKEEDP 

       610        620        630        640        650        660 
FNVDSSSLTG PVADTNLDFF QSDPFVGSDP FKDDPFGKID PFGGDPFKGS DPFASDCFFR 

       670        680        690        700        710        720 
QSTDPFATSS TDPFSAANNS SITSVETLKH NDPFAPGGTV VAASDSATDP FASVFGNESF 

       730        740        750        760        770        780 
GGGFADFSTL SKVNNEDPFR SATSSSVSNV VITKNVFEET SVKSEDEPPA LPPKIGTPTR 

       790        800        810        820        830        840 
PCPLPPGKRS INKLDSPDPF KLNDPFQPFP GNDSPKEKDP EIFCDPFTSA TTTTNKEADP 

       850        860        870        880        890 
SNFANFSAYP SEEDMIEWAK RESEREEEQR LARLNQQEQE DLELAIALSK SEISEA 

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References

« Hide 'large scale' references
[1]"The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32."
Wong W.T., Kraus M.H., Carlomagno F., Zelano A., Druck T., Croce C.M., Huebner K., di Fiore P.P.
Oncogene 9:1591-1597(1994) [PubMed: 8183552] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-822.
Tissue: Melanoma.
[2]"A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL."
Bernard O.A., Mauchauffe M., Mecucci C., van den Berghe H., Berger R.
Oncogene 9:1039-1045(1994) [PubMed: 8134107] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Eps15 in human umbilical vein endothelial cells."
Kronstein R., Grossklaus S., Schnittler H.-J.
Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins."
Matsuda M., Ota S., Tanimura R., Nakamura H., Matuoka K., Takenawa T., Nagashima K., Kurata T.
J. Biol. Chem. 271:14468-14472(1996) [PubMed: 8662907] [Abstract]
Cited for: INTERACTION WITH CRK.
[6]"Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis."
Chen H., Fre S., Slepnev V.I., Capua M.R., Takei K., Butler M.H., Di Fiore P.P., De Camilli P.
Nature 394:793-797(1998) [PubMed: 9723620] [Abstract]
Cited for: INTERACTION WITH EPN1.
[7]"TTP specifically regulates the internalization of the transferrin receptor."
Tosoni D., Puri C., Confalonieri S., Salcini A.E., De Camilli P., Tacchetti C., Di Fiore P.P.
Cell 123:875-888(2005) [PubMed: 16325581] [Abstract]
Cited for: INTERACTION WITH SH3BP4.
[8]"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules."
Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M.
Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-849, MASS SPECTROMETRY.
Tissue: Epithelium.
[9]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,