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Protein

Epidermal growth factor receptor substrate 15-like 1

Gene

EPS15L1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. 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 DAB2.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi172 – 184PROSITE-ProRule annotationAdd BLAST13

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • calcium ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Endocytosis

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000127527-MONOMER.
ReactomeiR-HSA-182971. EGFR downregulation.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.

Names & Taxonomyi

Protein namesi
Recommended name:
Epidermal growth factor receptor substrate 15-like 1
Alternative name(s):
Eps15-related protein
Short name:
Eps15R
Gene namesi
Name:EPS15L1
Synonyms:EPS15R
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:24634. EPS15L1.

Subcellular locationi

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • clathrin coat of coated pit Source: Ensembl
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Coated pit, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi58513.
OpenTargetsiENSG00000127527.
PharmGKBiPA134906266.

Polymorphism and mutation databases

BioMutaiEPS15L1.
DMDMi61223942.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001461182 – 864Epidermal growth factor receptor substrate 15-like 1Add BLAST863

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei74PhosphotyrosineBy similarity1
Modified residuei107PhosphoserineBy similarity1
Modified residuei108PhosphoserineCombined sources1
Modified residuei229PhosphoserineCombined sources1
Modified residuei244PhosphoserineCombined sources1
Modified residuei253PhosphoserineCombined sources1
Modified residuei255PhosphoserineCombined sources1
Modified residuei259PhosphoserineCombined sources1
Modified residuei362PhosphoserineBy similarity1
Modified residuei366PhosphothreonineCombined sources1
Modified residuei371PhosphoserineCombined sources1
Modified residuei374PhosphoserineCombined sources1
Modified residuei377PhosphoserineCombined sources1
Modified residuei560PhosphoserineCombined sources1
Modified residuei564PhosphotyrosineBy similarity1
Modified residuei577PhosphothreonineCombined sources1
Modified residuei593PhosphoserineCombined sources1
Modified residuei666PhosphoserineCombined sources1
Modified residuei672PhosphoserineCombined sources1
Modified residuei697PhosphoserineCombined sources1
Modified residuei717PhosphoserineCombined sources1
Modified residuei734PhosphoserineCombined sources1
Modified residuei793PhosphoserineCombined sources1
Modified residuei797PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues by EGFR.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9UBC2.
MaxQBiQ9UBC2.
PaxDbiQ9UBC2.
PeptideAtlasiQ9UBC2.
PRIDEiQ9UBC2.

PTM databases

iPTMnetiQ9UBC2.
PhosphoSitePlusiQ9UBC2.

Expressioni

Gene expression databases

BgeeiENSG00000127527.
CleanExiHS_EPS15L1.
ExpressionAtlasiQ9UBC2. baseline and differential.
GenevisibleiQ9UBC2. HS.

Organism-specific databases

HPAiHPA019237.
HPA055309.

Interactioni

Subunit structurei

Interacts with EPS15, AGFG1/HRB and AGFG2/HRBL. Associates with the clathrin-associated adapter protein complex 2 (AP-2) (By similarity). Interacts with FCHO1. Interacts with FCHO2. Interacts (via EH domains) with DAB2. Interacts with UBQLN1 (via ubiquitin-like domain).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GNG5P632183EBI-2556746,EBI-10220734
PRKCDBPQ969G52EBI-2556746,EBI-3893101
TRAPPC2P0DI813EBI-2556746,EBI-5663373
TRAPPC2P0DI81-34EBI-11958621,EBI-11961968

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL

Protein-protein interaction databases

BioGridi121840. 38 interactors.
IntActiQ9UBC2. 23 interactors.
MINTiMINT-1538779.
STRINGi9606.ENSP00000248070.

Structurei

3D structure databases

ProteinModelPortaliQ9UBC2.
SMRiQ9UBC2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 104EH 1PROSITE-ProRule annotationAdd BLAST90
Domaini127 – 215EH 2PROSITE-ProRule annotationAdd BLAST89
Domaini159 – 194EF-handPROSITE-ProRule annotationAdd BLAST36
Domaini275 – 365EH 3PROSITE-ProRule annotationAdd BLAST91
Repeati618 – 62013
Repeati640 – 64223
Repeati645 – 64733
Repeati650 – 65243
Repeati656 – 65853
Repeati661 – 66363
Repeati667 – 66973
Repeati685 – 68783
Repeati690 – 69293
Repeati709 – 711103
Repeati728 – 730113
Repeati754 – 756123
Repeati806 – 808133
Repeati812 – 814143
Repeati833 – 835153

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 368Interaction with DAB2By similarityAdd BLAST354
Regioni618 – 83515 X 3 AA repeats of D-P-FAdd BLAST218

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili386 – 553Sequence analysisAdd BLAST168

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi750 – 816Pro-richAdd BLAST67

Sequence similaritiesi

Contains 1 EF-hand domain.PROSITE-ProRule annotation
Contains 3 EH domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG0998. Eukaryota.
ENOG410XTDR. LUCA.
GeneTreeiENSGT00760000118985.
HOGENOMiHOG000004804.
HOVERGENiHBG005591.
InParanoidiQ9UBC2.
KOiK12472.
OMAiQKNSALY.
OrthoDBiEOG091G01RG.
PhylomeDBiQ9UBC2.
TreeFamiTF324293.

Family and domain databases

Gene3Di1.10.238.10. 3 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000261. EH_dom.
[Graphical view]
PfamiPF12763. EF-hand_4. 3 hits.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
SM00027. EH. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 3 hits.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 4 hits.
PS50031. EH. 3 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UBC2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAPLIPLSQ QIPTGNSLYE SYYKQVDPAY TGRVGASEAA LFLKKSGLSD
60 70 80 90 100
IILGKIWDLA DPEGKGFLDK QGFYVALRLV ACAQSGHEVT LSNLNLSMPP
110 120 130 140 150
PKFHDTSSPL MVTPPSAEAH WAVRVEEKAK FDGIFESLLP INGLLSGDKV
160 170 180 190 200
KPVLMNSKLP LDVLGRVWDL SDIDKDGHLD RDEFAVAMHL VYRALEKEPV
210 220 230 240 250
PSALPPSLIP PSKRKKTVFP GAVPVLPASP PPKDSLRSTP SHGSVSSLNS
260 270 280 290 300
TGSLSPKHSL KQTQPTVNWV VPVADKMRFD EIFLKTDLDL DGYVSGQEVK
310 320 330 340 350
EIFMHSGLTQ NLLAHIWALA DTRQTGKLSK DQFALAMYFI QQKVSKGIDP
360 370 380 390 400
PQVLSPDMVP PSERGTPGPD SSGSLGSGEF TGVKELDDIS QEIAQLQREK
410 420 430 440 450
YSLEQDIREK EEAIRQKTSE VQELQNDLDR ETSSLQELEA QKQDAQDRLD
460 470 480 490 500
EMDQQKAKLR DMLSDVRQKC QDETQMISSL KTQIQSQESD LKSQEDDLNR
510 520 530 540 550
AKSELNRLQQ EETQLEQSIQ AGRVQLETII KSLKSTQDEI NQARSKLSQL
560 570 580 590 600
HESRQEAHRS LEQYDQVLDG AHGASLTDLA NLSEGVSLAE RGSFGAMDDP
610 620 630 640 650
FKNKALLFSN NTQELHPDPF QTEDPFKSDP FKGADPFKGD PFQNDPFAEQ
660 670 680 690 700
QTTSTDPFGG DPFKESDPFR GSATDDFFKK QTKNDPFTSD PFTKNPSLPS
710 720 730 740 750
KLDPFESSDP FSSSSVSSKG SDPFGTLDPF GSGSFNSAEG FADFSQMSKP
760 770 780 790 800
PPSGPFTSSL GGAGFSDDPF KSKQDTPALP PKKPAPPRPK PPSGKSTPVS
810 820 830 840 850
QLGSADFPEA PDPFQPLGAD SGDPFQSKKG FGDPFSGKDP FVPSSAAKPS
860
KASASGFADF TSVS
Length:864
Mass (Da):94,255
Last modified:May 1, 2000 - v1
Checksum:iF4126069F6E00387
GO
Isoform 2 (identifier: Q9UBC2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     863-864: VS → FGNEEQQLAWAKRESEKAEQERLARLRRQEQEDLELAIALSKADMPAA

Show »
Length:910
Mass (Da):99,606
Checksum:iF56CC554F539B5FE
GO
Isoform 3 (identifier: Q9UBC2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     750-864: PPPSGPFTSS...SGFADFTSVS → VKVHL

Show »
Length:754
Mass (Da):83,248
Checksum:i5FFC0740FA78FC8B
GO
Isoform 4 (identifier: Q9UBC2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     598-601: DDPF → VKVE
     602-864: Missing.

Note: No experimental confirmation available.
Show »
Length:601
Mass (Da):66,479
Checksum:i9709A5D16D1E126A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti680K → E in BAG59115 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046904598 – 601DDPF → VKVE in isoform 4. 1 Publication4
Alternative sequenceiVSP_046905602 – 864Missing in isoform 4. 1 PublicationAdd BLAST263
Alternative sequenceiVSP_045429750 – 864PPPSG…FTSVS → VKVHL in isoform 3. 2 PublicationsAdd BLAST115
Alternative sequenceiVSP_042200863 – 864VS → FGNEEQQLAWAKRESEKAEQ ERLARLRRQEQEDLELAIAL SKADMPAA in isoform 2. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110265 mRNA. Translation: AAF21930.1.
AB015346 mRNA. Translation: BAA88118.1.
AK024166 mRNA. Translation: BAG51266.1.
AK296473 mRNA. Translation: BAG59115.1.
AC008764 Genomic DNA. No translation available.
AC020917 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84542.1.
BC131590 mRNA. Translation: AAI31591.1.
BC142716 mRNA. Translation: AAI42717.1.
CCDSiCCDS32944.1. [Q9UBC2-1]
CCDS58653.1. [Q9UBC2-3]
CCDS58654.1. [Q9UBC2-2]
CCDS59363.1. [Q9UBC2-4]
RefSeqiNP_001245303.1. NM_001258374.1. [Q9UBC2-2]
NP_001245304.1. NM_001258375.1. [Q9UBC2-3]
NP_001245305.1. NM_001258376.1. [Q9UBC2-4]
NP_067058.1. NM_021235.2. [Q9UBC2-1]
UniGeneiHs.654639.
Hs.683428.
Hs.744842.

Genome annotation databases

EnsembliENST00000248070; ENSP00000248070; ENSG00000127527. [Q9UBC2-1]
ENST00000455140; ENSP00000393313; ENSG00000127527. [Q9UBC2-2]
ENST00000535753; ENSP00000440103; ENSG00000127527. [Q9UBC2-3]
ENST00000597937; ENSP00000472267; ENSG00000127527. [Q9UBC2-4]
ENST00000602022; ENSP00000471981; ENSG00000127527. [Q9UBC2-3]
GeneIDi58513.
KEGGihsa:58513.
UCSCiuc002ndx.5. human. [Q9UBC2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110265 mRNA. Translation: AAF21930.1.
AB015346 mRNA. Translation: BAA88118.1.
AK024166 mRNA. Translation: BAG51266.1.
AK296473 mRNA. Translation: BAG59115.1.
AC008764 Genomic DNA. No translation available.
AC020917 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84542.1.
BC131590 mRNA. Translation: AAI31591.1.
BC142716 mRNA. Translation: AAI42717.1.
CCDSiCCDS32944.1. [Q9UBC2-1]
CCDS58653.1. [Q9UBC2-3]
CCDS58654.1. [Q9UBC2-2]
CCDS59363.1. [Q9UBC2-4]
RefSeqiNP_001245303.1. NM_001258374.1. [Q9UBC2-2]
NP_001245304.1. NM_001258375.1. [Q9UBC2-3]
NP_001245305.1. NM_001258376.1. [Q9UBC2-4]
NP_067058.1. NM_021235.2. [Q9UBC2-1]
UniGeneiHs.654639.
Hs.683428.
Hs.744842.

3D structure databases

ProteinModelPortaliQ9UBC2.
SMRiQ9UBC2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121840. 38 interactors.
IntActiQ9UBC2. 23 interactors.
MINTiMINT-1538779.
STRINGi9606.ENSP00000248070.

PTM databases

iPTMnetiQ9UBC2.
PhosphoSitePlusiQ9UBC2.

Polymorphism and mutation databases

BioMutaiEPS15L1.
DMDMi61223942.

Proteomic databases

EPDiQ9UBC2.
MaxQBiQ9UBC2.
PaxDbiQ9UBC2.
PeptideAtlasiQ9UBC2.
PRIDEiQ9UBC2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000248070; ENSP00000248070; ENSG00000127527. [Q9UBC2-1]
ENST00000455140; ENSP00000393313; ENSG00000127527. [Q9UBC2-2]
ENST00000535753; ENSP00000440103; ENSG00000127527. [Q9UBC2-3]
ENST00000597937; ENSP00000472267; ENSG00000127527. [Q9UBC2-4]
ENST00000602022; ENSP00000471981; ENSG00000127527. [Q9UBC2-3]
GeneIDi58513.
KEGGihsa:58513.
UCSCiuc002ndx.5. human. [Q9UBC2-1]

Organism-specific databases

CTDi58513.
DisGeNETi58513.
GeneCardsiEPS15L1.
HGNCiHGNC:24634. EPS15L1.
HPAiHPA019237.
HPA055309.
neXtProtiNX_Q9UBC2.
OpenTargetsiENSG00000127527.
PharmGKBiPA134906266.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0998. Eukaryota.
ENOG410XTDR. LUCA.
GeneTreeiENSGT00760000118985.
HOGENOMiHOG000004804.
HOVERGENiHBG005591.
InParanoidiQ9UBC2.
KOiK12472.
OMAiQKNSALY.
OrthoDBiEOG091G01RG.
PhylomeDBiQ9UBC2.
TreeFamiTF324293.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000127527-MONOMER.
ReactomeiR-HSA-182971. EGFR downregulation.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.

Miscellaneous databases

ChiTaRSiEPS15L1. human.
GeneWikiiEPS15L1.
GenomeRNAii58513.
PROiQ9UBC2.

Gene expression databases

BgeeiENSG00000127527.
CleanExiHS_EPS15L1.
ExpressionAtlasiQ9UBC2. baseline and differential.
GenevisibleiQ9UBC2. HS.

Family and domain databases

Gene3Di1.10.238.10. 3 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000261. EH_dom.
[Graphical view]
PfamiPF12763. EF-hand_4. 3 hits.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
SM00027. EH. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 3 hits.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 4 hits.
PS50031. EH. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEP15R_HUMAN
AccessioniPrimary (citable) accession number: Q9UBC2
Secondary accession number(s): A2RRF3, A5PL29, B4DKA3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Studies in clathrin-mediated endocytosis used a siRNA mixture of EPS15 and EPS15L1.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.