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Q5R4H4 (EPS8_PONAB) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 60. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Epidermal growth factor receptor kinase substrate 8
Gene names
Name:EPS8
OrganismPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) [Reference proteome]
Taxonomic identifier9601 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo

Protein attributes

Sequence length822 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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 DFNB31 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 By similarity.

Subunit structure

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 DFNB31 By similarity.

Subcellular location

Cytoplasmcell cortex By similarity. Cell projectionruffle membrane By similarity. Cell projectiongrowth cone By similarity. Cell projectionstereocilium By similarity. Cell junctionsynapsesynaptosome By similarity. Note: Localizes to the midzone of dividing cells By similarity.

Domain

The effector region is required for activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. It mediates both barbed-end actin capping and actin bundling activities. 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 By similarity.

The SH3 domain mediates interaction with SHB By similarity.

Post-translational modification

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 By similarity.

Phosphorylation at Ser-625 and Thr-629 by MAPK following BDNF treatment promotes removal from actin and filopodia formation. Phosphorylated by several receptor tyrosine kinases By similarity.

Sequence similarities

Belongs to the EPS8 family.

Contains 1 PH domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Membrane
Synapse
Synaptosome
   DomainSH3 domain
   LigandActin-binding
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRac protein signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

actin crosslink formation

Inferred from sequence or structural similarity. Source: UniProtKB

actin filament bundle assembly

Inferred from sequence or structural similarity. Source: UniProtKB

actin polymerization-dependent cell motility

Inferred from sequence or structural similarity. Source: UniProtKB

barbed-end actin filament capping

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

exit from mitosis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of actin filament length

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell shape

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell cortex

Inferred from sequence or structural similarity. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

growth cone

Inferred from electronic annotation. Source: UniProtKB-SubCell

ruffle membrane

Inferred from sequence or structural similarity. Source: UniProtKB

stereocilium

Inferred from sequence or structural similarity. Source: UniProtKB

synapse

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionRac GTPase binding

Inferred from sequence or structural similarity. Source: UniProtKB

actin binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 822822Epidermal growth factor receptor kinase substrate 8
PRO_0000086996

Regions

Domain69 – 12961PH; first part
Domain381 – 41434PH; second part
Domain531 – 59060SH3
Region649 – 822174Effector region By similarity
Region680 – 69819Amphipathic helix By similarity
Region718 – 73821Helix bundle 1 By similarity
Region752 – 7576Helix bundle 2 By similarity
Region762 – 7676Helix bundle 3 By similarity
Region766 – 78520Helix bundle 4 By similarity
Compositional bias615 – 65137Pro-rich

Amino acid modifications

Modified residue3171Phosphothreonine By similarity
Modified residue4761Phosphoserine By similarity
Modified residue6251Phosphoserine; by MAPK By similarity
Modified residue6291Phosphothreonine; by MAPK By similarity
Modified residue6591Phosphoserine By similarity

Experimental info

Sequence conflict411A → V in CAH90029. Ref.1
Sequence conflict2701V → A in CAH90029. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q5R4H4 [UniParc].

Last modified April 3, 2013. Version 2.
Checksum: 32ABBCDE17505774

FASTA82291,972
        10         20         30         40         50         60 
MNGHISNHPS SFEMYPSQMN GYGSSPTFSQ MDREHGSKTS AKALYEQRKN YARDSVSSVS 

        70         80         90        100        110        120 
DISQYRVEHL TTFVLDRKDA MITVDDGIRK LKLLDAKGKV WTQDMILQVD DRAVSLIDLE 

       130        140        150        160        170        180 
SKNELENFPL NTIQHCQAVM HSCSYDSVLA LVCKEPTQNK PDLHLFQCDE VKANLISEDI 

       190        200        210        220        230        240 
ESAISDSKGG KQKRRPDALR MISNADPGIP PPPRAPAPAP PGTVTQVDVR SRVAAWSAWA 

       250        260        270        280        290        300 
ADQGDFEKPR QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR 

       310        320        330        340        350        360 
KKNKKGKRKG PGEGVLTLRA KPPPPDEFLD CFQKFKHGFN LLAKLKSHIQ NPSAADLVHF 

       370        380        390        400        410        420 
LFTPLNMVVQ ATGGPELASS VLSPLLNKDT IDFLNYTVNG DERQLWMSLG GTWTKARAEW 

       430        440        450        460        470        480 
PKEQFIPPYV PRFRNGWEPP MLNFMGATME QDLYQLAESV ANVAEHQRKQ EIKRLSTEHS 

       490        500        510        520        530        540 
SVSEYHPADG YAFSSNIYTR GSHLDQGEAA VAFKPTSNRH IDRNYEPLKT QPKKYAKSKY 

       550        560        570        580        590        600 
DFVARNNSEL SVLKDDILEI LDDRKQWWKV RNASGDSGFV PNNILDIVRP PESGLGRADP 

       610        620        630        640        650        660 
PYTHTIQKQR MEYGPRPADT PPAPSPPPTP APVPVPLPPS TPAPVPVSKF PANITRQNSS 

       670        680        690        700        710        720 
SSDSGGSIVR DSQRHKQLPV DRRKSQMEEV QDELIHRLTI GRSAAQKKFH VPRQNVPVIN 

       730        740        750        760        770        780 
ITYDSTPEDV KTWLQSKGFN PVTVNSLGVL NGAQLFSLNK DELRTVCPEG ARVYSQITVQ 

       790        800        810        820 
KAALEDSSGS SELQEIMRRR QEKISAAASD SGVESFDEGS SH 

« Hide

References

[1]The German cDNA consortium
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain cortex and Kidney.
[2]"A 6x draft sequence assembly of the Pongo pygmaeus abelii genome."
Wilson R.K., Mardis E.
Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CR857764 mRNA. Translation: CAH90029.1.
CR861274 mRNA. Translation: CAH93342.1.
ABGA01225282 Genomic DNA. No translation available.
ABGA01225283 Genomic DNA. No translation available.
ABGA01225284 Genomic DNA. No translation available.
ABGA01225285 Genomic DNA. No translation available.
ABGA01225286 Genomic DNA. No translation available.
ABGA01225287 Genomic DNA. No translation available.
ABGA01225288 Genomic DNA. No translation available.
ABGA01225289 Genomic DNA. No translation available.
ABGA01225290 Genomic DNA. No translation available.
ABGA01225291 Genomic DNA. No translation available.
ABGA01225292 Genomic DNA. No translation available.
ABGA01225293 Genomic DNA. No translation available.
ABGA01225294 Genomic DNA. No translation available.
ABGA01225295 Genomic DNA. No translation available.
ABGA01225296 Genomic DNA. No translation available.
ABGA01225297 Genomic DNA. No translation available.
ABGA01225298 Genomic DNA. No translation available.
ABGA01225299 Genomic DNA. No translation available.
ABGA01225300 Genomic DNA. No translation available.
RefSeqNP_001127655.1. NM_001134183.1.
UniGenePab.1694.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEQ5R4H4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSPPYT00000033390; ENSPPYP00000024127; ENSPPYG00000004333.
GeneID100174737.
KEGGpon:100174737.

Organism-specific databases

CTD2059.

Phylogenomic databases

GeneTreeENSGT00390000003646.
HOVERGENHBG003090.
InParanoidQ5R4H4.
KOK17277.
OrthoDBEOG7TMZR9.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR011993. PH_like_dom.
IPR013625. PTB.
IPR006020. PTB/PI_dom.
IPR001452. SH3_domain.
[Graphical view]
PfamPF08416. PTB. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTSM00462. PTB. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
PROSITEPS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameEPS8_PONAB
AccessionPrimary (citable) accession number: Q5R4H4
Secondary accession number(s): K7EUA3, Q5RDX8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: April 3, 2013
Last modified: April 16, 2014
This is version 60 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families