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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: 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 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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

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
Proteomesi
  • UP000001595 Componentsi: Chromosome 12, Unassembled WGS sequence

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000869961 – 822Epidermal growth factor receptor kinase substrate 8Add BLAST822

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei58PhosphoserineBy similarity1
Modified residuei223PhosphothreonineBy similarity1
Modified residuei317PhosphothreonineBy similarity1
Modified residuei476PhosphoserineBy similarity1
Modified residuei625Phosphoserine; by MAPKBy similarity1
Modified residuei629Phosphothreonine; by MAPKBy similarity1
Modified residuei659PhosphoserineBy similarity1
Modified residuei662PhosphoserineBy similarity1
Modified residuei685PhosphoserineBy similarity1
Modified residuei811PhosphoserineBy similarity1
Modified residuei815PhosphoserineBy similarity1

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).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).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 WHRN (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9601.ENSPPYP00000004948.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini69 – 129PH; first partAdd BLAST61
Domaini381 – 414PH; second partAdd BLAST34
Domaini531 – 590SH3PROSITE-ProRule annotationAdd BLAST60

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni649 – 822Effector regionBy similarityAdd BLAST174
Regioni680 – 698Amphipathic helixBy similarityAdd BLAST19
Regioni718 – 738Helix bundle 1By similarityAdd BLAST21
Regioni752 – 757Helix bundle 2By similarity6
Regioni762 – 767Helix bundle 3By similarity6
Regioni766 – 785Helix bundle 4By similarityAdd BLAST20

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi615 – 651Pro-richAdd BLAST37

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).By similarity
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.
HOVERGENiHBG003090.
InParanoidiQ5R4H4.
KOiK17277.

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.

Q5R4H4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNGHISNHPS SFEMYPSQMN GYGSSPTFSQ MDREHGSKTS AKALYEQRKN
60 70 80 90 100
YARDSVSSVS DISQYRVEHL TTFVLDRKDA MITVDDGIRK LKLLDAKGKV
110 120 130 140 150
WTQDMILQVD DRAVSLIDLE SKNELENFPL NTIQHCQAVM HSCSYDSVLA
160 170 180 190 200
LVCKEPTQNK PDLHLFQCDE VKANLISEDI ESAISDSKGG KQKRRPDALR
210 220 230 240 250
MISNADPGIP PPPRAPAPAP PGTVTQVDVR SRVAAWSAWA ADQGDFEKPR
260 270 280 290 300
QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR
310 320 330 340 350
KKNKKGKRKG PGEGVLTLRA KPPPPDEFLD CFQKFKHGFN LLAKLKSHIQ
360 370 380 390 400
NPSAADLVHF LFTPLNMVVQ ATGGPELASS VLSPLLNKDT IDFLNYTVNG
410 420 430 440 450
DERQLWMSLG GTWTKARAEW PKEQFIPPYV PRFRNGWEPP MLNFMGATME
460 470 480 490 500
QDLYQLAESV ANVAEHQRKQ EIKRLSTEHS SVSEYHPADG YAFSSNIYTR
510 520 530 540 550
GSHLDQGEAA VAFKPTSNRH IDRNYEPLKT QPKKYAKSKY DFVARNNSEL
560 570 580 590 600
SVLKDDILEI LDDRKQWWKV RNASGDSGFV PNNILDIVRP PESGLGRADP
610 620 630 640 650
PYTHTIQKQR MEYGPRPADT PPAPSPPPTP APVPVPLPPS TPAPVPVSKF
660 670 680 690 700
PANITRQNSS SSDSGGSIVR DSQRHKQLPV DRRKSQMEEV QDELIHRLTI
710 720 730 740 750
GRSAAQKKFH VPRQNVPVIN ITYDSTPEDV KTWLQSKGFN PVTVNSLGVL
760 770 780 790 800
NGAQLFSLNK DELRTVCPEG ARVYSQITVQ KAALEDSSGS SELQEIMRRR
810 820
QEKISAAASD SGVESFDEGS SH
Length:822
Mass (Da):91,972
Last modified:April 3, 2013 - v2
Checksum:i32ABBCDE17505774
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41A → V in CAH90029 (Ref. 1) Curated1
Sequence conflicti270V → A in CAH90029 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
XP_009245788.1. XM_009247513.1.
UniGeneiPab.1694.

Genome annotation databases

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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
XP_009245788.1. XM_009247513.1.
UniGeneiPab.1694.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9601.ENSPPYP00000004948.

Proteomic databases

PRIDEiQ5R4H4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2059.

Phylogenomic databases

eggNOGiKOG3557. Eukaryota.
ENOG410XT9R. LUCA.
GeneTreeiENSGT00390000003646.
HOVERGENiHBG003090.
InParanoidiQ5R4H4.
KOiK17277.

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_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: November 30, 2016
This is version 74 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

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.