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Protein

Epidermal growth factor receptor kinase substrate 8

Gene

Eps8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin-based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2-dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with WHRN and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes.9 Publications

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • Rac GTPase binding Source: UniProtKB
  • signaling adaptor activity Source: InterPro

GO - Biological processi

  • actin crosslink formation Source: UniProtKB
  • actin cytoskeleton reorganization Source: MGI
  • actin filament bundle assembly Source: UniProtKB
  • actin polymerization-dependent cell motility Source: UniProtKB
  • adult locomotory behavior Source: MGI
  • barbed-end actin filament capping Source: UniProtKB
  • behavioral response to ethanol Source: MGI
  • dendritic cell migration Source: UniProtKB
  • exit from mitosis Source: UniProtKB
  • Rac protein signal transduction Source: UniProtKB
  • regulation of actin filament length Source: UniProtKB
  • regulation of cell shape Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Actin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Epidermal growth factor receptor kinase substrate 8
Gene namesi
Name:Eps8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:104684. Eps8.

Subcellular locationi

GO - Cellular componenti

  • brush border Source: UniProtKB
  • cell cortex Source: UniProtKB
  • cell junction Source: UniProtKB-KW
  • extracellular exosome Source: MGI
  • growth cone Source: UniProtKB-SubCell
  • NMDA selective glutamate receptor complex Source: MGI
  • postsynaptic density Source: MGI
  • ruffle membrane Source: UniProtKB
  • stereocilium Source: UniProtKB
  • synapse Source: MGI
  • vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Defects in PDGF-induced membrane ruffling due to defects in Ras to Rac signals. Dendritic cells are impaired in directional and chemotactic migration and are delayed in reaching the draining lymph node in vivo after inflammatory challenge. Mice show short stereocilia.3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi624S → A: Does not detach from actin following BDNF treatment; when associated with A-628. 1 Publication1
Mutagenesisi624S → E: Mimicks phosphorylation state; promotes detachment from actin in absence of BDNF treatment; when associated with E-628. 1 Publication1
Mutagenesisi628T → A: Does not detach from actin following BDNF treatment; when associated with A-624. 1 Publication1
Mutagenesisi628T → E: Mimicks phosphorylation state; promotes detachment from actin in absence of BDNF treatment; when associated with E-624. 1 Publication1
Mutagenesisi689V → D: Abolishes barbed-end actin-binding without affecting actin bundling activity. 1 Publication1
Mutagenesisi693L → D: Abolishes barbed-end actin-binding without affecting actin bundling activity. 1 Publication1
Mutagenesisi706R → A: Impairs both actin capping and bundling activities. 1 Publication1
Mutagenesisi708F → A: Impairs both actin capping and bundling activities. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000869951 – 821Epidermal growth factor receptor kinase substrate 8Add BLAST821

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei58PhosphoserineBy similarity1
Modified residuei223PhosphothreonineBy similarity1
Modified residuei317PhosphothreonineCombined sources1
Modified residuei475PhosphoserineBy similarity1
Modified residuei624Phosphoserine; by MAPK1 Publication1
Modified residuei628Phosphothreonine; by MAPK1 Publication1
Modified residuei658PhosphoserineCombined sources1
Modified residuei661PhosphoserineCombined sources1
Modified residuei684PhosphoserineCombined sources1
Modified residuei810PhosphoserineCombined sources1
Modified residuei814PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated by the SCF(FBXW5) E3 ubiquitin-protein ligase complex during G2 phase, leading to its transient degradation and subsequent cell shape changes required to allow mitotic progression. Reappears at the midzone of dividing cells.1 Publication
Phosphorylation at Ser-624 and Thr-628 by MAPK following BDNF treatment promotes removal from actin and filopodia formation. Phosphorylated by several receptor tyrosine kinases.2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ08509.
MaxQBiQ08509.
PaxDbiQ08509.
PeptideAtlasiQ08509.
PRIDEiQ08509.

PTM databases

iPTMnetiQ08509.
PhosphoSitePlusiQ08509.

Expressioni

Tissue specificityi

Expressed in neuronal cell body and neurites, and prominently enriched in the axonal growth cone.1 Publication

Gene expression databases

BgeeiENSMUSG00000015766.
ExpressionAtlasiQ08509. baseline and differential.
GenevisibleiQ08509. MM.

Interactioni

Subunit structurei

Homodimer. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with BAIAP2. Interacts with SHB and LANCL1. Interacts with EGFR; mediates EPS8 phosphorylation. Interacts with MYO15A and WHRN.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ABI1Q8IZP02EBI-375596,EBI-375446From a different organism.
Abi1Q8CBW32EBI-375596,EBI-375511
BAIAP2Q9UQB88EBI-375596,EBI-525456From a different organism.
LANCL1O438132EBI-375596,EBI-3046631From a different organism.

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • Rac GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi199491. 8 interactors.
DIPiDIP-32858N.
IntActiQ08509. 7 interactors.
MINTiMINT-1506131.
STRINGi10090.ENSMUSP00000052776.

Structurei

Secondary structure

1821
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi534 – 539Combined sources6
Beta strandi556 – 559Combined sources4
Helixi561 – 563Combined sources3
Beta strandi566 – 570Combined sources5
Beta strandi576 – 580Combined sources5
Helixi581 – 583Combined sources3
Beta strandi584 – 587Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AOJX-ray2.50A/B532-591[»]
1I07X-ray1.80A/B532-591[»]
1I0CX-ray2.00A/B532-591[»]
ProteinModelPortaliQ08509.
SMRiQ08509.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ08509.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini69 – 129PH; first partAdd BLAST61
Domaini381 – 414PH; second partAdd BLAST34
Domaini532 – 591SH3PROSITE-ProRule annotationAdd BLAST60

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni648 – 821Effector regionAdd BLAST174
Regioni679 – 697Amphipathic helixAdd BLAST19
Regioni717 – 737Helix bundle 1Add BLAST21
Regioni751 – 756Helix bundle 26
Regioni761 – 766Helix bundle 36
Regioni765 – 784Helix bundle 4Add BLAST20

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi210 – 213Poly-Pro4
Compositional biasi322 – 325Poly-Pro4
Compositional biasi421 – 440Pro-richAdd BLAST20
Compositional biasi620 – 650Pro-richAdd BLAST31
Compositional biasi658 – 663Poly-Ser6

Domaini

The effector region is required for activating the Rac-specific guanine nucleotide exchange factor (GEF) activity (PubMed:11524436). It mediates both barbed-end actin capping and actin bundling activities (PubMed:20532239). The capping activity is mediated by an amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers, while the bundling activity is mediated by a compact 4 helix bundle, which contacts 3 actin subunits along the filament (PubMed:20532239).2 Publications
The SH3 domain mediates interaction with SHB.By similarity

Sequence similaritiesi

Belongs to the EPS8 family.Curated
Contains 1 PH domain.Curated
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG3557. Eukaryota.
ENOG410XT9R. LUCA.
GeneTreeiENSGT00390000003646.
HOGENOMiHOG000060324.
HOVERGENiHBG003090.
InParanoidiQ08509.
KOiK17277.
OMAiAEWPKEQ.
OrthoDBiEOG091G023T.
TreeFamiTF313069.

Family and domain databases

CDDicd01210. PTB_EPS8. 1 hit.
Gene3Di2.30.29.30. 1 hit.
InterProiIPR030222. EPS8.
IPR033928. EPS8_PTB.
IPR011993. PH_dom-like.
IPR013625. PTB.
IPR006020. PTB/PI_dom.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR12287:SF21. PTHR12287:SF21. 1 hit.
PfamiPF08416. PTB. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTiSM00462. PTB. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50002. SH3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q08509-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNGHMSNRSS GYGVYPSQLN GYGSSPPYSQ MDREHSSRTS AKALYEQRKN
60 70 80 90 100
YARDSVSSVS DVSQYRVEHL TTFVLDRKDA MITVEDGIRK LKLLDAKGKV
110 120 130 140 150
WTQDMILQVD DRAVSLIDLE SKNELENFPL NTISHCQAVV HACSYDSILA
160 170 180 190 200
LVCKEPTQSK PDLHLFQCDE VKANLISEDI ESAISDSKGG KQKRRPEALR
210 220 230 240 250
MIAKADPGIP PPPRAPAPVP PGTVTQVDVR SRVAAWSAWA ADQGDFEKPR
260 270 280 290 300
QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR
310 320 330 340 350
KKSKKSKRKG PGEGVLTLRA KPPPPDEFVD CFQKFKHGFN LLAKLKSHIQ
360 370 380 390 400
NPSASDLVHF LFTPLNMVVQ ATGGPELASS VLSPLLTKDT VDFLNYTATA
410 420 430 440 450
EERKLWMSLG DSWVKVRAEW PKEQFIPPYV PRFRNGWEPP MLNFMGAPTE
460 470 480 490 500
QDMYQLAESV ANAEHQRKQD SKRLSTEHSN VSDYPPADGY AYSSSMYHRG
510 520 530 540 550
PHADHGEAAM PFKSTPNHQV DRNYDAVKTQ PKKYAKSKYD FVARNSSELS
560 570 580 590 600
VMKDDVLEIL DDRRQWWKVR NASGDSGFVP NNILDIMRTP ESGVGRADPP
610 620 630 640 650
YTHTIQKQRT EYGLRSADTP SAPSPPPTPA PVPVPLPPSV PAPVSVPKVP
660 670 680 690 700
ANVTRQNSSS SDSGGSIVRD SQRYKQLPVD RRKSQMEEVQ DELFQRLTIG
710 720 730 740 750
RSAAQRKFHV PRQNVPVINI TYDSSPEEVK TWLQSKGFNP VTVNSLGVLN
760 770 780 790 800
GAQLFSLNKD ELRSVCPEGA RVFNQITVQK AALEDSNGSS ELQEIMRRRQ
810 820
EKISAAASDS GVESFDEGSS H
Length:821
Mass (Da):91,737
Last modified:July 27, 2011 - v2
Checksum:i50F691FAC3EF1304
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti652N → D in AAA16358 (PubMed:8404850).Curated1
Sequence conflicti652N → D in AAH16890 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L21671 mRNA. Translation: AAA16358.1.
AK149683 mRNA. Translation: BAE29023.1.
AK166156 mRNA. Translation: BAE38601.1.
BC016890 mRNA. Translation: AAH16890.1.
CCDSiCCDS20665.1.
PIRiS39983.
RefSeqiNP_001258516.1. NM_001271587.1.
NP_001258517.1. NM_001271588.1.
NP_001258518.1. NM_001271589.1.
NP_001258524.1. NM_001271595.1.
NP_031971.2. NM_007945.3.
XP_011239506.1. XM_011241204.2.
UniGeneiMm.235346.
Mm.412332.

Genome annotation databases

EnsembliENSMUST00000058210; ENSMUSP00000052776; ENSMUSG00000015766.
ENSMUST00000100841; ENSMUSP00000098402; ENSMUSG00000015766.
ENSMUST00000111878; ENSMUSP00000107509; ENSMUSG00000015766.
GeneIDi13860.
KEGGimmu:13860.
UCSCiuc009emz.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L21671 mRNA. Translation: AAA16358.1.
AK149683 mRNA. Translation: BAE29023.1.
AK166156 mRNA. Translation: BAE38601.1.
BC016890 mRNA. Translation: AAH16890.1.
CCDSiCCDS20665.1.
PIRiS39983.
RefSeqiNP_001258516.1. NM_001271587.1.
NP_001258517.1. NM_001271588.1.
NP_001258518.1. NM_001271589.1.
NP_001258524.1. NM_001271595.1.
NP_031971.2. NM_007945.3.
XP_011239506.1. XM_011241204.2.
UniGeneiMm.235346.
Mm.412332.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AOJX-ray2.50A/B532-591[»]
1I07X-ray1.80A/B532-591[»]
1I0CX-ray2.00A/B532-591[»]
ProteinModelPortaliQ08509.
SMRiQ08509.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199491. 8 interactors.
DIPiDIP-32858N.
IntActiQ08509. 7 interactors.
MINTiMINT-1506131.
STRINGi10090.ENSMUSP00000052776.

PTM databases

iPTMnetiQ08509.
PhosphoSitePlusiQ08509.

Proteomic databases

EPDiQ08509.
MaxQBiQ08509.
PaxDbiQ08509.
PeptideAtlasiQ08509.
PRIDEiQ08509.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000058210; ENSMUSP00000052776; ENSMUSG00000015766.
ENSMUST00000100841; ENSMUSP00000098402; ENSMUSG00000015766.
ENSMUST00000111878; ENSMUSP00000107509; ENSMUSG00000015766.
GeneIDi13860.
KEGGimmu:13860.
UCSCiuc009emz.2. mouse.

Organism-specific databases

CTDi2059.
MGIiMGI:104684. Eps8.

Phylogenomic databases

eggNOGiKOG3557. Eukaryota.
ENOG410XT9R. LUCA.
GeneTreeiENSGT00390000003646.
HOGENOMiHOG000060324.
HOVERGENiHBG003090.
InParanoidiQ08509.
KOiK17277.
OMAiAEWPKEQ.
OrthoDBiEOG091G023T.
TreeFamiTF313069.

Miscellaneous databases

EvolutionaryTraceiQ08509.
PROiQ08509.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000015766.
ExpressionAtlasiQ08509. baseline and differential.
GenevisibleiQ08509. MM.

Family and domain databases

CDDicd01210. PTB_EPS8. 1 hit.
Gene3Di2.30.29.30. 1 hit.
InterProiIPR030222. EPS8.
IPR033928. EPS8_PTB.
IPR011993. PH_dom-like.
IPR013625. PTB.
IPR006020. PTB/PI_dom.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR12287:SF21. PTHR12287:SF21. 1 hit.
PfamiPF08416. PTB. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTiSM00462. PTB. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEPS8_MOUSE
AccessioniPrimary (citable) accession number: Q08509
Secondary accession number(s): Q3TM41
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.