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Q5R4H4

- EPS8_PONAB

UniProt

Q5R4H4 - EPS8_PONAB

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Protein
Epidermal growth factor receptor kinase substrate 8
Gene
EPS8
Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at transcript 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 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.

GO - Molecular functioni

  1. Rac GTPase binding Source: UniProtKB
  2. actin binding Source: UniProtKB

GO - Biological processi

  1. Rac protein signal transduction Source: UniProtKB
  2. actin crosslink formation Source: UniProtKB
  3. actin filament bundle assembly Source: UniProtKB
  4. actin polymerization-dependent cell motility Source: UniProtKB
  5. barbed-end actin filament capping Source: UniProtKB
  6. dendritic cell migration Source: UniProtKB
  7. exit from mitosis Source: UniProtKB
  8. regulation of actin filament length Source: UniProtKB
  9. 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
OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Taxonomic identifieri9601 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
ProteomesiUP000001595: Chromosome 12

Subcellular locationi

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.

GO - Cellular componenti

  1. cell cortex Source: UniProtKB
  2. cell junction Source: UniProtKB-KW
  3. growth cone Source: UniProtKB-SubCell
  4. ruffle membrane Source: UniProtKB
  5. stereocilium Source: UniProtKB
  6. synapse Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 822822Epidermal growth factor receptor kinase substrate 8
PRO_0000086996Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei317 – 3171Phosphothreonine By similarity
Modified residuei476 – 4761Phosphoserine By similarity
Modified residuei625 – 6251Phosphoserine; by MAPK By similarity
Modified residuei629 – 6291Phosphothreonine; by MAPK By similarity
Modified residuei659 – 6591Phosphoserine By similarity

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 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.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ5R4H4.

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 DFNB31 By similarity.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini69 – 12961PH; first part
Add
BLAST
Domaini381 – 41434PH; second part
Add
BLAST
Domaini531 – 59060SH3
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni649 – 822174Effector region By similarity
Add
BLAST
Regioni680 – 69819Amphipathic helix By similarity
Add
BLAST
Regioni718 – 73821Helix bundle 1 By similarity
Add
BLAST
Regioni752 – 7576Helix bundle 2 By similarity
Regioni762 – 7676Helix bundle 3 By similarity
Regioni766 – 78520Helix bundle 4 By similarity
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi615 – 65137Pro-rich
Add
BLAST

Domaini

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.

Sequence similaritiesi

Belongs to the EPS8 family.
Contains 1 PH domain.
Contains 1 SH3 domain.

Keywords - Domaini

SH3 domain

Phylogenomic databases

GeneTreeiENSGT00390000003646.
HOVERGENiHBG003090.
InParanoidiQ5R4H4.
KOiK17277.
OrthoDBiEOG7TMZR9.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_like_dom.
IPR013625. PTB.
IPR006020. PTB/PI_dom.
IPR001452. SH3_domain.
[Graphical view]
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.
PROSITEiPS50002. SH3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5R4H4-1 [UniParc]FASTAAdd to Basket

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MNGHISNHPS SFEMYPSQMN GYGSSPTFSQ MDREHGSKTS AKALYEQRKN    50
YARDSVSSVS DISQYRVEHL TTFVLDRKDA MITVDDGIRK LKLLDAKGKV 100
WTQDMILQVD DRAVSLIDLE SKNELENFPL NTIQHCQAVM HSCSYDSVLA 150
LVCKEPTQNK PDLHLFQCDE VKANLISEDI ESAISDSKGG KQKRRPDALR 200
MISNADPGIP PPPRAPAPAP PGTVTQVDVR SRVAAWSAWA ADQGDFEKPR 250
QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR 300
KKNKKGKRKG PGEGVLTLRA KPPPPDEFLD CFQKFKHGFN LLAKLKSHIQ 350
NPSAADLVHF LFTPLNMVVQ ATGGPELASS VLSPLLNKDT IDFLNYTVNG 400
DERQLWMSLG GTWTKARAEW PKEQFIPPYV PRFRNGWEPP MLNFMGATME 450
QDLYQLAESV ANVAEHQRKQ EIKRLSTEHS SVSEYHPADG YAFSSNIYTR 500
GSHLDQGEAA VAFKPTSNRH IDRNYEPLKT QPKKYAKSKY DFVARNNSEL 550
SVLKDDILEI LDDRKQWWKV RNASGDSGFV PNNILDIVRP PESGLGRADP 600
PYTHTIQKQR MEYGPRPADT PPAPSPPPTP APVPVPLPPS TPAPVPVSKF 650
PANITRQNSS SSDSGGSIVR DSQRHKQLPV DRRKSQMEEV QDELIHRLTI 700
GRSAAQKKFH VPRQNVPVIN ITYDSTPEDV KTWLQSKGFN PVTVNSLGVL 750
NGAQLFSLNK DELRTVCPEG ARVYSQITVQ KAALEDSSGS SELQEIMRRR 800
QEKISAAASD SGVESFDEGS SH 822
Length:822
Mass (Da):91,972
Last modified:April 3, 2013 - v2
Checksum:i32ABBCDE17505774
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti41 – 411A → V in CAH90029. 1 Publication
Sequence conflicti270 – 2701V → A in CAH90029. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
RefSeqiNP_001127655.1. NM_001134183.1.
UniGeneiPab.1694.

Genome annotation databases

EnsembliENSPPYT00000033390; ENSPPYP00000024127; ENSPPYG00000004333.
GeneIDi100174737.
KEGGipon:100174737.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
RefSeqi NP_001127655.1. NM_001134183.1.
UniGenei Pab.1694.

3D structure databases

ModBasei Search...
MobiDBi Search...

Proteomic databases

PRIDEi Q5R4H4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSPPYT00000033390 ; ENSPPYP00000024127 ; ENSPPYG00000004333 .
GeneIDi 100174737.
KEGGi pon:100174737.

Organism-specific databases

CTDi 2059.

Phylogenomic databases

GeneTreei ENSGT00390000003646.
HOVERGENi HBG003090.
InParanoidi Q5R4H4.
KOi K17277.
OrthoDBi EOG7TMZR9.

Family and domain databases

Gene3Di 2.30.29.30. 1 hit.
InterProi IPR011993. PH_like_dom.
IPR013625. PTB.
IPR006020. PTB/PI_dom.
IPR001452. SH3_domain.
[Graphical view ]
Pfami PF08416. PTB. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view ]
SMARTi SM00462. PTB. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 1 hit.
PROSITEi PS50002. SH3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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].

Entry informationi

Entry nameiEPS8_PONAB
AccessioniPrimary (citable) accession number: Q5R4H4
Secondary accession number(s): K7EUA3, Q5RDX8
Entry historyi
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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi